1.FGF2 confers chemo-resistance of breast cancer cells by activating Akt-mTOR signal
Yixue GU ; Xiaoting JIA ; Liyun LUO ; Guopei ZHENG ; Zhimin HE
The Journal of Practical Medicine 2017;33(1):36-40
] Objective To explore the role and mechanisms of FGF2 in chemo?resistance in breast cancer. Methods The inhibitors for different signal pathway were used to treat two drug?resistant breast cancer cell lines MCF?7/5?Fu and T47D/5?Fu established in our lab. MTS assay was used to determine chemo?sensitivity and Hoechst stain was used to measure apoptosis. Protein activation and FGF2 protein level in cell culture medium were detected by western blot and ELISA respectively. Results Akt inhibitor MK?2206 (20 nM) and mTOR inhibitor AZD8055 (2 nM) significantly reversed the chemo?resistance of MCF?7/5?Fu and T47D/5?Fu cell lines to 5?Fu and paclitaxel, but ERK1/2 inhibitor SCH772984 showed no significant effect. Compared to parent cell lines MCF?7 and T47D, p?Akt and p?S6K (represented as mTORactivity) levels were obviously up?regulated in MCF?7/5?Fu and T47D/5?Fu cell lines, and so do the FGF2 mRNA level and FGF2 protein level from culture medium. Moreover, FGFR inhibitor AZD4547 (4 nM) markedly reversed the chemo?resistance of MCF?7/5?Fu and T47D/5?Fu cell lines to 5?Fu and paclitaxel and down?regulated activation of FGFR?Akt?mTOR signal pathway. In agreement, FGF2 protein (10ng/ml) enhanced the chemo?resistance of MCF?7 and T47D cell lines to 5?Fu and paclitaxel and up?regulated activation of FGFR?Akt?mTOR signal pathway. Conclusion Activation of FGF2?FGFR?Akt?mTOR signal pathway promoted chemo?resistance of breast cancer cells.
2.Effects and mechanisms of histone deacetylase inhibitors on invasion and metastasis of Her2 positive breast cancer cell
Jiang YIN ; Hao LIU ; Guopei ZHENG ; Yixue GU ; Zhimin HE
Journal of Chinese Physician 2017;19(2):177-181
Objective To investigate the effect of histone deacetylase inhibitor on Her2 positive breast cancer cell line BT474 and SKBR3 in apoptosis and metastasis.Methods Histone deacetylase inhibitor MS-275,suberoylanilide hydroxamic acid (SAHA)(4 μmol/L,and 50 μmol/iL,respectively) treated the cell lines BT474 and SKBR3 cells.Flow cytometer examined the apoptosis ratio.Transwell tested their metastatic activity.Western blot assay was performed to detect the associated proteins.Results SAHA and MS-275 inhibited the cell survival.The BT474 cell survival was (39 ± 11) %,(54 ± 8) %,and the SKBR3 survival was (62 ± 6) %,(71 ± 9) %,according to the fluorescence-activated cell sorting (FACS) result.SAHA and MS-275 induced the BT474 cell apoptosis 8.46± 0.28 (P <0.01),4.15 ± 0.71 (P <0.01) fold change,respectively;and upregulated the SKBR3 cell apoptosis ratio 5.51 ± 1.24 (P <0.01),4.04 ±0.69 (P <0.01) fold.The Transwell result showed that SAHA,MS-275 inhibited the Transwell ability of BT474 from the control 184.7 ± 18.8 to 104.3 ± 7.1,131.3 ±9.1 per view,and the SKBR3 from control 60 ± 16.7 per view to 14.3 ± 6.5,34.3 ± 8.7 per view.The Western blot result showed that SAHA,MS-275 inhibited the protein level of vimentin,Her2,β-catenin,histone deacetylase inhibitor (HDACi),and upregulated the acetylation level of histone 3.The E-caherin protein was regulated in BT474 and SKBR3 cells.Conclusions MS-275,SAHA can induce BT474 and SKBR3 apoptosis significantly,also inhibit their metastatic activity.
3.Clinical efficacy of ambroxol intravenous and budesonide atomizing inhalation combined with cefodizime on infantile pneumonia
Yan WANG ; Lizhu CHEN ; Yixue ZHENG ; Jiekui CHEN
Chinese Journal of Biochemical Pharmaceutics 2016;36(6):88-90
Objective To investigate the clinical efficacy of ambroxol intravenous and budesonide atomizing inhalation combined with cefodizime on infantile pneumonia and its effects of serum PCT, IL -6 levels and related immune factors.Methods 95 children with pneumonia from May 2013 to October 2015 in Sanya Hospital of Traditional Chinese Medicine were collected and randomly divided into control group(n=47) and experiment group (n=48), two groups were treated by clinical routine treatment, such as antipyretic, anti-inflammatory, strengthen nutrition in children, and control group were added with ambroxol, iv, qd; experiment group were added cefodizime on the basis of control group, the course was one week.Clinical efficacy,serum PCT, IL -6 levels, immune factors and adverse reactions were observed and compared.Results The serum PCT and IL -6 levels of experiment group were lower than control group post-treatment, and CD4 +, CD4 +/CD8 +levels were higher than control group, CD8 +level was lower than control group, the differences were all significant (P<0.05).The effective rate of experiment group was 93.75%, higher than 80.85% of control group(P<0.05).Incidence of adverse reactions between two groups had no statistical difference.Conclusion Ambroxol intravenous and budesonide atomizing inhalation combine with cefodizime in treatment of infantile pneumonia has better clinical efficacy, could effectively reduce the serum PCT and IL-6 levels, effectively improve the clinical symptoms.
4.Clinical efficacy of extended hepatectomy for types III and IV hilar cholangiocarcinoma
Dongdong WANG ; Wanliang SUN ; Zheng LU ; Xiang MA ; Hua WU ; Jie GUO ; Yixue SUN ; Yang ZHANG ; Peiyuan CUI
Chinese Journal of Clinical Oncology 2016;43(6):250-254
Objective:To investigate the clinical efficacy of extended hepatectomy for hilar cholangiocarcinoma (HCCA) of Bismuth-Cor-lette typesⅢandⅣ(the longitudinal invasion degree along the biliary system is the main criteria). Methods:The clinical data of 61 patients with HCCA of Bismuth-Corlette types III and IV admitted in the Department of Hepatobiliary Surgery of the First Affiliated Hos-pital of Bengbu Medical College from January 2008 to May 2015 were analyzed retrospectively. Among the 61 cases, 22 underwent hepatectomy with half or over half of the liver removed or hepatic caudate lobectomy (regarded as the extended hepatectomy group), whereas 39 cases underwent irregular hepatectomy on the hepatic hilar region (regarded as the limited hepatectomy group). Results:Compared with those in the limited hepatectomy group, the patients in the extended hepatectomy group underwent longer duration of operation and experienced more bleeding during the procedure. The complication incidence rate for the extended hepatectomy group was lower than that for the limited hepatectomy group. No patient died during the perioperative period in the extended hepa-tectomy group, whereas two patients died in the limited hepatectomy group. Moreover, R0 resection was performed on 21 cases in the extended hepatectomy group, with a resection rate of (21/22) 95.5%, and on 20 cases in the limited hepatectomy group (P<0.05), with a resection rate of (20/39) 51.3%. Actuarial 1-, 3-, and 5-year survival rates were 77.27%, 36.36%, and 13.64%, respectively, in the extended hepatectomy group, and 69.23%, 20.51%, and 1.64%, respectively, in the limited hepatectomy group (P<0.05). Conclusion:Extended hepatectomy for patients with HCCA of Bismuth-Corlette typesⅢandⅣcould effectively increase the resection rates of R0 and the survival rate. Meanwhile, the prognosis of patients could be improved.
5.Experimental study of apoptosis induced by Talniflumate in breast cancer cells
Danqing HUANG ; Hongguang LIU ; Yongsheng CHEN ; Guopei ZHENG ; Yixue GU
Journal of Chinese Physician 2022;24(4):531-537
Objective:To explore the effect of the mucin modulator Talniflumate (Tal) on breast cancer cells and its synergistic effect after combined with the chemotherapy drug paclitaxel (PTX).Methods:The breast cancer cells were cultured in vitro. Lymphocyte proliferation activity assay (MTS) was used to detect the effects of different concentrations of Talniflumate alone and paclitaxel on the survival rate of breast cancer cells. The effects of the above drugs on the apoptosis of breast cancer cells were detected by flow cytometry. Western blot was used to detect the expression of glucosamine transferase (GCNT3) (the target of Talniflumate) in breast cancer cells before and after the treatment with Talniflumate. Transcriptome sequencing clarified the changes in related signaling pathways after treatment with Talniflumate. Results:Talniflumate promoted the apoptosis of breast cancer cells MCF7 and MDA-MB-231 cells in a concentration-dependent manner. The combination of Talniflumate and paclitaxel had a significant synergistic killing effect in MCF7 cells but not MDA-MB-231 cells. Western blot indicated that GCNT3 was highly expressed in MCF7 cells, while almost no expression in MDA-MB-231 cells; Talniflumate could reduce the expression of GCNT3 in MCF7 cells and after combined with paclitaxel, the expression of GCNT3 was downregulated more significantly. Transcriptome sequencing suggested that Talniflumate can regulate the expression of multiple signaling pathways such as TNF, p53, and SNARE.Conclusions:Talniflumate could induce apoptosis of breast cancer cell. Talniflumate combined with paclitaxel has a significant synergistic effect in killing tumor cells in breast cancer cells with high GCNT3 expression such as MCF7. The mechanism of Talniflumate induce apoptosis of breast cancer cells may be related to multiple signaling pathways such as TNF, p53, and SNARE.
6.APOBEC3B mediated the resistance to cisplatin in non-small cell lung carcinoma
Yongsheng CHEN ; Danqing HUANG ; Yixue GU ; Min DENG ; Huaping ZHOU ; Guopei ZHENG ; Zhimin HE
Journal of Chinese Physician 2020;22(5):662-666,673
Objective:APOBEC3B (A3B) is an important member of the apolipoprotein B mRNA editing enzyme catalytic polypeptide (APOBEC) family. The study aims to investigate the relationship between A3B expression and prognosis as well as resistance to cisplatin in non-small cell lung cancer (NSCLC).Methods:Real-time quantitative polymerase chain reaction (qRT-PCR) was used to analysis the A3B mRNA expression in 40 NSCLC tissues; Kaplan Meier plotter was used to analyse the correlation between A3B expression and clinical prognosis; in addition, the knock-down A3B expression cell line in human lung adenocarcinoma cell A549 was constructed; MTS and plate cloning experiment were performed to observe the changes in cell cisplatin sensitivity, and γ-H2AX immunofluorescence was used to quantitate the DNA damage.Results:Compared with adjacent tissues, A3B was highly expressed in NSCLC tissues (27/40). Kaplan Meier plotter analysis showed that A3B expression was positively correlated with NSCLC overall survival (OS) [adenocarcinoma: HR=0.64(0.47-0.86), P=0.002 6; squamous cell carcinoma: HR=0.77(0.59-1.01), P=0.006]. Cell-based studies showed that the knock-down A3B expression contributed to sensitivity to cisplatin in A549 cells. Conclusions:A3B mediates the sensitivity of lung cancer to cisplatin. This effect may partly explain why NSCLC patients with high A3B expression have a better prognosis.