1.Anticancer Activity of Diosgenin and Its Molecular Mechanism.
Qun-Li REN ; Qian WANG ; Xin-Qun ZHANG ; Miao WANG ; Huan HU ; Jun-Jie TANG ; Xiong-Tong YANG ; Ying-Hui RAN ; Huan-Huan LIU ; Zhi-Xing SONG ; Jian-Guo LIU ; Xiao-Lan LI
Chinese journal of integrative medicine 2023;29(8):738-749
Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.
Male
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Humans
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Carcinoma, Squamous Cell/drug therapy*
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Diosgenin/metabolism*
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Mouth Neoplasms/drug therapy*
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Apoptosis
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Prostatic Neoplasms/drug therapy*
2.Luteolin suppresses oral carcinoma 3 (OC3) cell growth and migration via modulating polo-like kinase 1 (PLK1) expression and cellular energy metabolism.
Pengfei GAO ; Wentao ZHANG ; Yujie LIN ; Ruijie LU ; Zijian LOU ; Gang LU ; Ruolang PAN ; Yunfang CHEN
Journal of Zhejiang University. Science. B 2023;24(12):1151-1158
Oral squamous cell carcinoma (OSCC) is a prevalent malignant tumor affecting the head and neck region (Leemans et al., 2018). It is often diagnosed at a later stage, leading to a poor prognosis (Muzaffar et al., 2021; Li et al., 2023). Despite advances in OSCC treatment, the overall 5-year survival rate of OSCC patients remains alarmingly low, falling below 50% (Jehn et al., 2019; Johnson et al., 2020). According to statistics, only 50% of patients with oral cancer can be treated with surgery. Once discovered, it is more frequently at an advanced stage. In addition, owing to the aggressively invasive and metastatic characteristics of OSCC, most patients die within one year of diagnosis. Hence, the pursuit of novel therapeutic drugs and treatments to improve the response of oral cancer to medication, along with a deeper understanding of their effects, remains crucial objectives in oral cancer research (Johnson et al., 2020; Bhat et al., 2021; Chen et al., 2023; Ruffin et al., 2023).
Humans
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Mouth Neoplasms/pathology*
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Carcinoma, Squamous Cell/metabolism*
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Luteolin/therapeutic use*
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Squamous Cell Carcinoma of Head and Neck/drug therapy*
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Head and Neck Neoplasms/drug therapy*
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Cell Line, Tumor
3.Investigation of apoptosis mechanism of arsenic trioxide on oral squamous cell carcinoma.
Chinese Journal of Stomatology 2003;38(1):20-23
OBJECTIVETo probe the possible mechanism of growth-inhibitory and apoptosis of oral squamous cell carcinoma by arsenic trioxide.
METHODSThe induction of apoptosis in two tongue squamous carcinoma cells treated by arsenic trioxide was investigated. The morphology changes of the cells was observed under electron microscope. The mitochondrial transmembrane potential was detected using rhodamine 123 and flow cytometry. The cell cycle was detected by flow cytometry, and p16, p53, BCL-2, Caspase-3, and PARP changes were examined by western blot.
RESULTS1. The antiproliferative effect on the oral squamous carcinoma cells by arsenic trioxide was carried out through two ways: induction of apoptosis and toxicity damage. 2. Activation of the caspase-3 and PARP, while no changes of p16, p53, BCL-2 occurred. 3. Mitochondrial transmembrane potential collapse and G(2)-M stagnation were correlated with apoptosis of oral squamous cell carcinoma.
CONCLUSIONS1. Tubulins and mitochondria may be the chief action position of arsenic trioxide, which is the start-up factors of mechanism. 2. Activation of the caspase-3 proteolytic pathway may be one of the pivotal ways of apoptosis procedure induced by arsenic trioxide.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Blotting, Western ; Carcinoma, Squamous Cell ; drug therapy ; metabolism ; pathology ; Caspase 3 ; Caspases ; metabolism ; Cell Cycle ; drug effects ; DNA, Neoplasm ; drug effects ; metabolism ; Flow Cytometry ; Humans ; Intracellular Membranes ; drug effects ; physiology ; Membrane Potentials ; drug effects ; Mitochondria ; drug effects ; physiology ; Mouth Neoplasms ; drug therapy ; metabolism ; pathology ; Oxides ; pharmacology ; Poly(ADP-ribose) Polymerases ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Tumor Cells, Cultured ; drug effects ; ultrastructure ; Tumor Suppressor Protein p53 ; metabolism
4.The Bacterial Protein Azurin Enhances Sensitivity of Oral Squamous Carcinoma Cells to Anticancer Drugs.
Jeong Hae CHOI ; Moo Hyung LEE ; Yun Jung CHO ; Bong Soo PARK ; Shin KIM ; Gyoo Cheon KIM
Yonsei Medical Journal 2011;52(5):773-778
PURPOSE: Surgical therapy is the primary treatment for oral cancer, but it can cause facial distortion. Therefore, if anticancer drugs are effective against oral cancer, they may be used preferentially. However, oral squamous carcinoma cells (OSCCs) are resistant to these drugs, so finding a way to enhance the sensitivity of these cells to anticancer drugs is important. The bacterial protein azurin is known to selectively enter cancer cells and induce apoptosis. In this study, we show the anticancer effect of azurin in OSCC. MATERIALS AND METHODS: OSCC cell line (YD-9) was subjected to azurin treatment. Cell viability, morphology and protein expression levels were monitored after treatment of azurin. Cells were also subjected to combination treatment of azurin with either 5-fluorouracil or etopside. RESULTS: Azurin-treated cells showed decreased cell viability accompanied by apoptotic phenotypes including morphological change, DNA breakage, and increases in p53 and cyclin B1 protein levels. Combination treatment of azurin with other anti-tumor agents caused an increase in sensitivity to anticancer drugs in azurin-treated YD-9 cells. CONCLUSION: Azurin has a strong synergistic anticancer effect on oral cancer cells when it is used along with anticancer drugs.
Antineoplastic Agents/*administration & dosage
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Apoptosis/drug effects
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Azurin/*administration & dosage/genetics
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Carcinoma, Squamous Cell/*drug therapy/metabolism/pathology
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Cell Line, Tumor
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Cyclin B1/metabolism
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Drug Synergism
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Etoposide/administration & dosage
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Fluorouracil/administration & dosage
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Humans
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Mouth Neoplasms/*drug therapy/metabolism/pathology
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Tumor Suppressor Protein p53/metabolism
5.Pseudomonas aeruginosa Exotoxin A Reduces Chemoresistance of Oral Squamous Carcinoma Cell via Inhibition of Heat Shock Proteins 70 (HSP70).
Sang Rye PARK ; Kyoung Duk LEE ; Uk Kyu KIM ; Young Gi GIL ; Kyu Seon OH ; Bong Soo PARK ; Gyoo Cheon KIM
Yonsei Medical Journal 2010;51(5):708-716
PURPOSE: Oral squamous carcinoma (OSCC) cells exhibit resistance to chemotherapeutic agent-mediated apoptosis in the late stage of malignancy. Increased levels of heat shock proteins 70 (HSP70) in cancer cells are known to confer resistance to apoptosis. Since recent advances in the understanding of bacterial toxins have produced new strategies for the treatment of cancers, we investigated the effect of Pseudomonas aeruginosa exotoxin A (PEA) on HSP70 expression and induction of apoptosis in chemoresistant OSCC cell line (YD-9). MATERIALS AND METHODS: The apoptotic effect of PEA on chemoresistant YD-9 cells was confirmed by MTT, Hoechst and TUNEL stains, DNA electrophoresis, and Western blot analysis. RESULTS: While YD-9 cells showed high resistance to chemotherapeutic agents such as etoposide and 5-fluorouraci (5-FU), HSP70 antisense oligonucelotides sensitized chemoresistant YD-9 cells to etoposide and 5-FU. On the other hand, PEA significantly decreased the viability of YD-9 cells by deteriorating the HSP70-relating protecting system through inhibition of HSP70 expression and inducing apoptosis in YD-9 cells. Apoptotic manifestations were evidenced by changes in nuclear morphology, generation of DNA fragmentation, and activation of caspases. While p53, p21, and E2F-1 were upregulated, cdk2 and cyclin B were downregulated by PEA treatment, suggesting that PEA caused cell cycle arrest at the G2/M checkpoint. CONCLUSION: Therefore, these results indicate that PEA reduced the chemoresistance through inhibition of HSP70 expression and also induced apoptosis in chemoresistant YD-9 cells.
ADP Ribose Transferases/*pharmacology
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Antineoplastic Agents/*pharmacology
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Apoptosis/drug effects
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Bacterial Toxins/*pharmacology
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Blotting, Western
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Carcinoma, Squamous Cell/drug therapy/*metabolism
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Cell Cycle/drug effects
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Cell Line, Tumor
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Chromatography, Liquid
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Cyclin B/metabolism
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Cyclin-Dependent Kinase 2/metabolism
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Drug Resistance, Neoplasm/*drug effects
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E2F1 Transcription Factor/metabolism
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Electrophoresis
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Exotoxins/*pharmacology
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HSP70 Heat-Shock Proteins/genetics/*metabolism
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Humans
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In Situ Nick-End Labeling
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Mouth Neoplasms/drug therapy/*metabolism
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Tandem Mass Spectrometry
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Tumor Suppressor Protein p53/metabolism
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Virulence Factors/*pharmacology
6.Celecoxib enhances chemosensitivity of oral cancer cells by blocking cell cycle progression in vitro.
Wenxiao LIAO ; Yixuan YAN ; Yanqing HUANG ; Weizhong LI
Journal of Southern Medical University 2013;33(6):885-888
OBJECTIVETo investigate the effect of celecoxib in enhancing the chemosensitivity of oral cancer cells and the correlation of this effect with cell cycle arrest.
METHODSKB/VCR cell line was treated with celecoxib (10, 20, 40, and 80 µmol/L) and/or VCR (0.375, 0.75, 1.5, and 3 µmol/L), and the growth inhibition rates of KB/VCR cells were assessed with MTT assay. Flow cytometry was employed to analyze the distribution of cell cycle. Western blotting was performed to detect the expression of P-glycoprotein (P-gp) and the cell cycle related proteins Cyclin D1 and p21(WAF1/CIP1).
RESULTSLow concentrations of celecoxib (<20 µmol/L) produced no obvious effect on the proliferation of the cells. But at 10 µmol/L, celecoxib significantly enhanced the toxicity of VCR in a time-dependent manner, and the combined treatments for 24, 48, and 72 h caused growth inhibition rates of (37.53∓2.05)%, (46.67∓3.17)% and (54.02∓1.53)%, respectively, significantly higher than those following treatments with celecoxib or VCR alone (P<0.01). Compared with the cells treated with VCR alone , the cells with combined treatments showed a significantly increased cell percentage in G0/G1 phase [(56.08∓0.46)%] with decrease percentages in S phase [(22.83∓0.20)%] and G2/M phase [(21.09%∓0.66)%]. The combined treatment also significantly down-regulated cyclin D1, up-regulated p21(WAF1/CIP1), and reduced P-gp expressions in the cells.
CONCLUSIONSCelecoxib enhances the chemosensitivity of KB/VCR cells by down-regulating P-gp expression, which is partially mediated by modification of cyclin D1 and p21(WAF1/CIP1) to result in cell cycle arrest.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Celecoxib ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Drug Resistance, Neoplasm ; drug effects ; Humans ; KB Cells ; Mouth Neoplasms ; drug therapy ; metabolism ; Pyrazoles ; pharmacology ; Sulfonamides ; pharmacology
7.p53 gene therapy for oral cancer.
Chinese Journal of Stomatology 2012;47(9):569-572
Adenoviridae
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genetics
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Animals
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Apoptosis
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drug effects
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Carcinoma, Squamous Cell
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genetics
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metabolism
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therapy
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Cell Cycle
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drug effects
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Clinical Trials as Topic
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Genes, p53
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Genetic Therapy
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Genetic Vectors
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Humans
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Mouth Neoplasms
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genetics
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metabolism
;
therapy
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Mutation
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Tumor Suppressor Protein p53
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genetics
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metabolism
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Viral Vaccines
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pharmacology
;
therapeutic use
8.Clinical analysis of 51 cases of oral mucosal melanoma.
Chuan-zheng SUN ; Fu-jin CHEN ; Ming SONG ; Yu-e JIANG ; An-kui YANG ; Yan-feng CHEN
Chinese Journal of Stomatology 2011;46(9):528-530
OBJECTIVETo investigate the treatment and prognosis of the patients with oral mucosal melanoma (OMM).
METHODSThe clinicopathological and follow-up data of patients with OMM in Sun Yat-sen University Cancer Center from January 1976 to December 2005 were analyzed retrospectively.
RESULTSFifty-one cases were analyzed. The pathological lymph node metastasis rate was 61% (31/51) and the affected sites were confined to level I(b)-III (94%). The overall three year and five yearsurvival rates were 35% and 21% respectively. No significant difference of three year and five year survival rates were found between the group of incisional biopsy and the group of excisional biopsy. The prognosis was not affected by pigmentation. The survival rate of the patients receiving surgery combined with biotherapy or biochemotherapy was significantly higher than that of the patients treated by other modalities (P = 0.003).
CONCLUSIONSIn patients with OMM, lymph node metastasis was mostly confined to level I(b)-III. Incisional biopsy and pigmentation were not associated with an unfavorable prognosis. The prognosis of the patients with OMM was poor and the patients may get a better prognosis by receiving surgery combined with biotherapy or biochemotherapy.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; BCG Vaccine ; therapeutic use ; Combined Modality Therapy ; Female ; Follow-Up Studies ; Humans ; Interferon-gamma ; therapeutic use ; Interleukin-2 ; therapeutic use ; Lung Neoplasms ; secondary ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Melanoma ; drug therapy ; pathology ; surgery ; Melanoma-Specific Antigens ; metabolism ; Middle Aged ; Mouth Mucosa ; pathology ; surgery ; Mouth Neoplasms ; drug therapy ; pathology ; surgery ; Retrospective Studies ; S100 Proteins ; metabolism ; Survival Rate
9.Intervention effect of an inducible nitric oxide synthase inhibitor on carcinogenesis of hamster cheek pouch carcinoma.
Zhao-hui YANG ; Wei-liang CHEN ; Hai-gang LI ; Jin-song LI ; Jian-guang WANG
West China Journal of Stomatology 2004;22(5):357-361
OBJECTIVETo observe the expression changes of VEGF, iNOS and the level of MVD and NO during the evolution of Golden hamster cheek pouch carcinogenesis. To study the effect of NO in carcinogenesis in the pouch of hamster, and to investigate the effect of NOS inhibitor L-NAME in interfering with carcinogenesis.
METHODS90 golden hamsters were divided into three groups: 40 in experiment group, 40 in control group and 10 in blank group. DMBA was painted on hamster's cheek pouch in experiment and control group, L-NAME was given to hamster in experiment group at the dose of 0.02 ml/g. Hamsters were killed at 6, 9, 12 and 16th weeks, respectively. The blank group was killed at the 16th week. SABC immunohistochemistry assay was used to detect the expression of iNOS, VEGF and factor VIII-related antigen. MVD was measured. The level of NO was measured by Spectrophotometry.
RESULTSThe difference between control group and experiment group at the 12th week and 16th week was observed. The difference of positive expression rate of iNOS in all group was significant and difference between blank group and control group was significant. The difference of positive expression rate of VEGF in all group was significant and difference between blank group and control group at the 12th and 16th week was significant; there was significant difference in every group MVD from the 6th week control group to the 16th week control. There were significant difference among the control group, except the 6th week of experiment and control group.
CONCLUSIONThere is an increased expression of iNOS and the level of NO, as well MVD during the evolution of Golden hamster cheek pouch carcinogenesis from slightly dysplasia to invasive carcinoma. NO plays an important role during the evolution of carcinogenesis, and iNOS inhibitor L-NAME can inhibit the carcinogenesis.
Animals ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; Cricetinae ; Enzyme Inhibitors ; pharmacology ; Mesocricetus ; Mouth Neoplasms ; drug therapy ; pathology ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase ; metabolism ; Nitric Oxide Synthase Type II ; antagonists & inhibitors ; Vascular Endothelial Growth Factor A ; metabolism
10.The study of cucurbitacin BE polylactic acid nanoparticles delivering cucurbitacin BE to metastasized cervical lymph nodes in mice with oral cancer.
Kai YANG ; Yuming WEN ; Changmei WANG
West China Journal of Stomatology 2003;21(6):477-480
OBJECTIVEThe aim of this study was to investigate the delivery of Cucurbitacin BE to cervical lymph nodes by peri-cancer submucosal injection of the average diameter 85 nm Cucurbitacin BE polylactic acid nanoparticles (CuBE-PLA-NP).
METHODSCervical lymph node metastasis model of mice oral cancer was established and CuBE-PLA-NP and CuBE were injected in peri-cancer submucosal of the mice respectively, the concentration in blood, heart, liver, spleen, lung, kidney and cervical lymph node were measured by high performance liquid chromatography at fifteen time points, Targeted cervical lymph nodes were evaluated by targeting index, selectivity index, targeting efficiency, relative targeting efficiency and ratio of maximum concentration.
RESULTS(1) The CuBE concentration in the cervical lymph nodes after CuBE-PLA-NP injection was far higher than that after CuBE injection at every time point, the CuBE duration in the cervical lymph nodes in CuBE-PLA-NP group was far longer than that in CuBE group; (2) The five targeted values of the cervical lymph nodes in CuBE-PLA-NP group was far higher than that in CuBE group; (3) The CuBE concentration in blood, heart, liver, spleen, lung and kidney in CuBE-PLA-NP group was far lower than that in CuBE group.
CONCLUSIONThe CuBE-PLA-NP can specifically deliver CuBE to the cervical lymph nodes by peri-cancer submucosal injection, increase CuBE concentration and duration in metastasized cervical lymph nodes, and decrease drug concentration of other organs.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacokinetics ; Carcinoma, Squamous Cell ; drug therapy ; surgery ; Cucurbitacins ; Delayed-Action Preparations ; Drug Carriers ; Drug Delivery Systems ; Female ; Lactic Acid ; administration & dosage ; pharmacokinetics ; Lymph Nodes ; metabolism ; pathology ; Lymphatic Metastasis ; Male ; Mice ; Mouth Neoplasms ; drug therapy ; surgery ; Nanotechnology ; Neck ; Particle Size ; Polyesters ; Polymers ; administration & dosage ; pharmacokinetics ; Triterpenes ; administration & dosage ; pharmacokinetics