Modern pharmacological studies have shown that Shengmai San has the effects of enhancing immunity and improving blood circulation, and Curcumae Longae Rhizoma(Jianghuang) has anti-inflammatory, anti-cancer, anti-oxidation and other functions. Shengmai San combined with Jianghuang is a new research direction in the study of anti-tumor of traditional Chinese medicines. The main treatment for nasopharyngeal carcinoma is radiation therapy, but radiation therapy can cause a variety of side effects, and it also changes the composition of the intestinal flora. In this study, the 16 s rDNA sequencing platform was used to perform macro-sequence sequencing of the intestinal flora samples of nude mice bearing the veins of Shengmai Jianghuang San, and then the results of intestinal flora data were analyzed to investigate the effect of Shengmai Jianghuang San on tumors. The results showed that Shengmai Jianghuang San combined with irradiation could enhance the therapeutic effect of tumor treatment. Radiation therapy would reduce the total number and diversity of intestinal flora in nude mice, and also change the structure of the flora. Shengmai Jianghuang San could protect the diversity of colonies, and also partially restore the colony imbalance caused by irradiation. This study provides a research idea for Shengmai Jianghuang San as a sensitizing adjuvant for radiotherapy of nasopharyngeal carcinoma.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Gastrointestinal Microbiome ; drug effects ; Mice ; Mice, Nude ; Nasopharyngeal Carcinoma ; radiotherapy ; Radiation Tolerance ; Radiation-Sensitizing Agents ; pharmacology

The wide application of artemisinins in the treatment of multiple cancers reflects the advantages of traditional Chinese medicine used in this field. The existing basic and clinical studies have revealed that artesunate can effectively suppress the malignant progression of breast cancer,colon cancer,leukemia,melanoma,ovarian cancer,prostate cancer,kidney cancer and various tumors in central nervous system. The pharmacological mechanisms of artesunate against cancers are reflected in many aspects,such as inhibiting tumor cell proliferation,invasion and metastasis,inducing tumor cell apoptosis and autophagy,regulating cell signal transduction and inhibiting tumor angiogenesis. Meanwhile,growing experimental evidences have indicated that artesunate has been used for the sensitization of radiotherapy with X-ray,β-ray,γ-ray and~(60)Co γ-ray,as well as chemotherapy with cisplatin,carboplatin and doxorubicin.This review collected basic and clinical studies on the sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy published on PubMed and CNKI during April 2000 and February 2019,and summarized the clinical positioning and application of artesunate,with the aim to provide a more comprehensive explanation on the sensitization effect of artesunate on anti-cancer radiotherapy and chemotherapy,and offer the inspiration and ideas for the development of radiotherapy and chemotherapy sensitizers,as well as cancer resistance reversal agents.
Artesunate/therapeutic use* ; Carboplatin/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Cisplatin/therapeutic use* ; Doxorubicin/therapeutic use* ; Humans ; Neoplasms/radiotherapy* ; Radiation-Sensitizing Agents/therapeutic use*

Locoregional failure is the most frequent pattern of failure in locally advanced head and neck cancer patients and it leads to death in most of the patients. Second primary tumors occurring in the other head and neck region reach up to almost 40% of long-term survivors. Recommended and preferred retreatment option in operable patients is salvage surgical resection, reporting a 5-year overall survival of up to 40%. However, because of tumor location, extent, and underlying comorbidities, salvage surgery is often limited and compromised by incomplete resection. Reirradiation with or without combined chemotherapy is an appropriate option for unresectable recurrence. Reirradiation is carefully considered with a case-by-case basis. Reirradiation protocol enrollment is highly encouraged prior to committing patient to an aggressive therapy. Radiation doses greater than 60 Gy are usually recommended for successful salvage. Despite recent technical improvement in intensity-modulated radiotherapy (IMRT), the use of concurrent chemotherapy, and the emergence of molecularly targeted agents, careful patient selection remain as the most paramount factor in reirradiation. Tumors that recur or persist despite aggressive prior chemoradiation therapy imply the presence of chemoradio-resistant clonogens. Treatment protocols that combine novel targeted radiosensitizing agents with conformal high precision radiation are required to overcome the resistance while minimizing toxicity. Recent large number of data showed that IMRT may provide better locoregional control with acceptable acute or chronic morbidities. However, additional prospective studies are required before a definitive conclusion can be drawn on safety and effectiveness of IMRT.
Clinical Protocols ; Comorbidity ; Drug Therapy ; Head and Neck Neoplasms* ; Head* ; Humans ; Neck ; Patient Selection* ; Prospective Studies ; Radiation-Sensitizing Agents ; Radiotherapy, Intensity-Modulated* ; Re-Irradiation* ; Recurrence ; Retreatment ; Survivors

Objective: To investigate the improving effect of astaxanthin (AST) on the sperm quality of rats with ornidazole (ORN)-induced oligoasthenozoospermiaand its action mechanism. METHODS: Forty adult male SD rats were equally randomized into groups A (solvent control), B (low-dose ORN ［400 mg/（kg·d）］), C (high-dose ORN ［800 mg/（kg·d）］), D (low-dose ORN ［400 mg/（kg·d）］ + AST ［20 mg/（kg·d）］), and E (high-dose ORN ［800 mg/（kg·d）］ + AST ［20 mg/（kg·d）］), all treated intragastrically for3 weeks.After treatment, the epididymal tails ononeside was taken for determination of sperm concentration and activity, and the epididymideson the other side harvested for measurement of the activities of GSH-Px, GR, CAT and SOD and the MDA contentin the homogenate. RESULTS: Compared with group A, sperm motilityin the epididymal tail andGSH-Px and SOD activities in theepididymiswere markedly decreased while the MDAcontent significantlyincreased in group B (P<0.05), spermmotility and concentrationin the epididymal tail, testisindex, and the activities of GSH-Px, GR, CAT and SOD in the epididymis were remarkably reduced while theMDA contentsignificantly increased in group C(P<0.05). In comparison with group B, group D showed markedly increased sperm motility (［45.3±8.7］% vs ［66.3±8.9］%, P<0.05) in the epididymal tail and SOD activity in the epididymis (［116.7±25.3］ U/mg prot vs ［146.1±23.8］ U/mg prot, P<0.05), decreased MDA content(［1.68±0.45］ nmol/mg prot vs ［1.19±0.42］ nmol/mg prot, P<0.05).Compared with group C, group Eexhibited significant increases in the weight gained (［89.0±9.5］ vs ［99.9±4.1］ %, P<0.05) and sperm motility (［17.9±3.5］% vs ［27.3±5.3］ %, P<0.05) but a decrease in the content of MDA (［2.03±0.30］ nmol/mg prot vs ［1.52±0.41］ nmol/mg prot, P<0.05). CONCLUSIONS AST can improve spermquality in rats with ORN-inducedoligoasthenozoospermia, which may be associated with its enhancing effect on the antioxidant capacity of the epididymis.
Animals ; Antioxidants ; pharmacology ; Asthenozoospermia ; prevention & control ; Epididymis ; drug effects ; metabolism ; Male ; Oligospermia ; prevention & control ; Ornidazole ; Oxidative Stress ; Protective Agents ; pharmacology ; Radiation-Sensitizing Agents ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sperm Count ; Sperm Motility ; Spermatozoa ; drug effects ; metabolism ; Xanthophylls ; pharmacology

PURPOSE: Breast cancer is an important cause of death among women. The development of radioresistance in breast cancer leads to recurrence after radiotherapy. Caffeic acid phenethyl ester (CAPE), a polyphenolic compound of honeybee propolis, is known to have anticancer properties. In this study, we examined whether CAPE enhanced the radiation sensitivity of MDA-MB-231 (estrogen receptor-negative) and T47D (estrogen receptor-positive) cell lines. METHODS: The cytotoxic effect of CAPE on MDA-MB-231 and T47D breast cancer cells was evaluated by performing an 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay. To assess clonogenic ability, MDA-MB-231 and T47D cells were treated with CAPE (1 µM) for 72 hours before irradiation, and then, a colony assay was performed. A comet assay was used to determine the number of DNA strand breaks at four different times. RESULTS: CAPE decreased the viability of both cell lines in a dose- and time-dependent manner. In the clonogenic assay, pretreatment of cells with CAPE before irradiation significantly reduced the surviving fraction of MDA-MB-231 cells at doses of 6 and 8 Gy. A reduction in the surviving fraction of T47D cells was observed relative to MDA-MB-231 at lower doses of radiation. Additionally, CAPE maintained radiation-induced DNA damage in T47D cells for a longer period than in MDA-MB-231 cells. CONCLUSION: Our results indicate that CAPE impairs DNA damage repair immediately after irradiation. The induction of radiosensitivity by CAPE in radioresistant breast cancer cells may be caused by prolonged DNA damage.
Breast Neoplasms* ; Breast* ; Cause of Death ; Cell Line ; Comet Assay ; DNA Damage* ; DNA* ; Estrogens* ; Female ; Humans ; Propolis ; Radiation Tolerance* ; Radiation-Sensitizing Agents ; Radiotherapy ; Recurrence

Overexpression of human epidermal growth factor receptor 2 (HER2) is found in about 20% of breast cancer patients. With treatment using trastuzumab, an anti-HER2 monoclonal antibody, systemic control is improved. Nonetheless, the incidence of brain metastasis does not be improved, rather seems to be increased in HER2-positive breast cancer. The mainstay treatment for brain metastases is radiotherapy. According to the number of metastatic lesions and performance status of patients, radiosurgery or whole brain radiotherapy can be performed. The concurrent use of a radiosensitizer further improves intracranial control. Due to its large molecular weight, trastuzumab has a limited ability to cross the blood-brain barrier. However, small tyrosine kinase inhibitors such as lapatinib, has been noted to be a promising agent that can be used as a radiosensitizer to affect HER2-positive breast cancer. This review will outline general management of brain metastases and will focus on preclinical findings regarding the radiosensitizing effect of small molecule HER2 targeting agents.
Biology* ; Blood-Brain Barrier ; Brain* ; Breast Neoplasms ; Epidermal Growth Factor* ; Humans* ; Incidence ; Molecular Weight ; Neoplasm Metastasis* ; Protein-Tyrosine Kinases ; Radiation-Sensitizing Agents ; Radiosurgery ; Radiotherapy ; Receptor, Epidermal Growth Factor* ; Receptor, erbB-2 ; Trastuzumab

OBJECTIVE: To explore the effects of 3-methyladenine (3-MA, an autophagy inhibitor) on sensitivities of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy and the underlying mechanisms.
 METHODS: Cell proliferation was examined by MTT and colony formation assay, while cell apoptosis was evaluated by annexin V/PI double staining and 2-(4-Amidinophenyl)-6-indolecarbamidine dihydrochloride (DAPI) staining. Mitochondrial membrane potential was measured by commercial kit (JC-1). The expression of endoplasmic reticulum stress (ERS)-related protein, glucose-regulated protein 78 (GRP78) and autophagy-related protein beclin1, microtubule-associated protein 1 light chain 3 (LC3) were examined by Western blot.
 RESULTS: Cisplatin (DDP), ionizing radiation (IR) or tunicamycin (TM) treatment obviously inhibited the proliferation of HONE-1 cells in a concentration-dependent and time-dependent manner. Compared with control group, pretreatment with 1 mmol/L of 3-MA significantly 
reduced cell viability and enhanced the apoptosis in the DDP (6.00 μmol/L), 4.00 Gy IR or TM (1.00 μmol/L) groups. There was no significant difference in the apoptosis between the DDP (5.8%) and 4Gy IR (6.7%) groups. Compared with the control group, protein levels of GRP78, beclin1 and lipid-conjugated membrane-bound form (LC3-II) were significantly increased after the treatment of DDP, 4.00 Gy IR or TM, which were inhibited by pretreatment of 3-MA.
 CONCLUSION 3-MA can sensitize HONE-1 cells to chemotherapy and radiotherapy, which is related to prevention of endoplasmic reticulum stress-induced autophagy in nasopharyngeal carcinoma cells.
Adenine ; analogs & derivatives ; pharmacology ; Apoptosis ; Apoptosis Regulatory Proteins ; metabolism ; Autophagy ; Beclin-1 ; Carcinoma ; Cell Line, Tumor ; drug effects ; radiation effects ; Cell Proliferation ; Cell Survival ; Cisplatin ; pharmacology ; Endoplasmic Reticulum Stress ; Heat-Shock Proteins ; metabolism ; Humans ; Membrane Potential, Mitochondrial ; Membrane Proteins ; metabolism ; Microtubule-Associated Proteins ; metabolism ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; pathology ; Radiation, Ionizing ; Radiation-Sensitizing Agents ; pharmacology ; Tunicamycin ; pharmacology

OBJECTIVETo study the radiosensitizing effect of resveratrol on hypopharyngeal carcinoma cell line FADU in vitro.

METHODSHypopharyngeal carcinoma cell line FADU was cultured in in vitro DMEM. Its inhibition on cell proliferation was detected using cytotoxicity test (MTT assay). The cell survival curve was drawn using clone formation to obtain sensitive enhancement ratio (SER). Changes of the cell cycle and cell apoptosis were analyzed using flow cytometry (FCM).

RESULTSResults of MTT showed the inhibition of resveratrol on FADU cells increased along with its concentrations (P < 0.05). Results of clone formation indicated the surviving fraction at 2 Gy (SF2) was 0.717 ± 0.062 in the irradiation group, and 0.426 ± 0.035 in the resveratrol plus irradiation group (with SER ranged 1.684 ± 0.178) with statistical difference (P = 0.007). Results of FCM showed that after radiation of 4 Gy radiation, cells at G2/M phase arrest increased, but cells at G1 decreased. After radiation of resveratrol for 24 h, cells at G1 decreased, but cells at G2/M phase and S phase arrest increased. When 4 Gy radiation combined resveratrol was used, cells at G2/M phase arrest significantly increased, but cells at G1 significantly decreased. The apoptosis rate was 1.94% ± 1.65% in the control group, 4.56% ± 0.92% in the irradiation group, 2.03% ± 1.46% in the resveratrol group, and 23.11% ± 7.22% in the resveratrol plus irradiation group. There was statistical difference between the resveratrol plus irradiation group and the rest 3 groups (P < 0.05).

CONCLUSIONResveratrol could enhance the radiosensitivity of hypopharyngeal carcinoma FADU cells in vitro possibly by inducing cell apoptosis and causing changes in the cell cycle distribution.

Apoptosis ; Carcinoma, Squamous Cell ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Head and Neck Neoplasms ; Humans ; Hypopharyngeal Neoplasms ; drug therapy ; Radiation Tolerance ; Radiation-Sensitizing Agents ; therapeutic use ; Stilbenes ; therapeutic use

PURPOSE: The purpose of this study was to evaluate whether an exogenous epidermal growth factor (EGF) could induce anti-tumor and radiosensitizing effects in vivo. MATERIALS AND METHODS: BALB/c-nu mice that were inoculated with A431 (human squamous cell carcinoma) cells in the right hind legs were divided into five groups: I (no treatment), II (EGF for 6 days), III (EGF for 20 days), IV (radiotherapy [RT]), and V (RT plus concomitant EGF). EGF was administered intraperitoneally (5 mg/kg) once a day and the RT dose was 30 Gy in six fractions. Hematoxylin and eosin (H&E) stained sections of tumor, liver, lung, and kidney tissues were investigated. Additionally, tumors were subjected to immunohistochemistry staining with caspase-3. RESULTS: EGF for 6 days decreased tumor volume, but it approached the level of the control group at the end of follow-up (p=0.550). The duration of tumor shrinkage was prolonged in group V while the slope of tumor re-growth phase was steeper in group IV (p=0.034). EGF for 20 days decreased tumor volume until the end of the observation period (p < 0.001). Immunohistochemistry revealed that mice in group V showed stronger intensity than those in group IV. There were no abnormal histological findings upon H&E staining of the normal organs. CONCLUSION: EGF-induced anti-tumor effect was ascertained in the xenograft mouse models with A431 cells. Concomitant use of EGF has the potential role as a radiosensitizer in the design of fractionated irradiation.
Animals ; Antineoplastic Agents ; Apoptosis ; Caspase 3 ; Eosine Yellowish-(YS) ; Epidermal Growth Factor* ; Follow-Up Studies ; Hematoxylin ; Heterografts* ; Immunohistochemistry ; Kidney ; Leg ; Liver ; Lung ; Mice* ; Radiation-Sensitizing Agents ; Tumor Burden ; Xenograft Model Antitumor Assays

PURPOSE: This study was conducted in order to validate the radiosensitization effect of valproic acid, a biologically available histone deacetylase inhibitor, for fractionated radiation. MATERIALS AND METHODS: Radiosensitization effect of valproic acid was tested for the A549 cell line and U87MG cell line in vitro. Fractionated irradiation of 12 Gy in four fractions was administered on D2-5 with valproic acid, 150 mg/Kg, ip, bid for six consecutive days (D1-6) to A549 and U87MG tumors implanted in BALB/c-nude mice. A growth delay curve was formulated. RESULTS: Radiosensitization effect of valproic acid was found for both cell lines; A549 at 1.5 mM and 3.0 mM concentration and U87MG at 3.0 mM concentration. In growth delay analysis, a statistically significant radiosensitization effect was observed for both tumors (p < 0.001 for both tumors). Difference for change in slope for control and valproic acid versus radiotherapy and radiotherapy plus valproic acid showed borderline significance for the U87MG cell line (p=0.065), indicating beyond additive effect, whereas this difference was statistically insignificant for A549 tumor (p=0.951), indicating additive effect. CONCLUSION: Results of this study indicate that a radiosensitizing effect for fractionated radiotherapy of valproic acid for A549 and U87MG tumors in vivo is evident and that it may be more than additive for U87MG tumors. Further exploitation of histone deacetylase inhibitors in clinical trials is warranted.
Animals ; Carcinoma, Non-Small-Cell Lung ; Cell Line ; Glioblastoma ; Histone Deacetylase Inhibitors ; Mice ; Radiation Tolerance ; Radiation-Sensitizing Agents* ; Radiotherapy ; Valproic Acid*