|
|
Effects of Berberine combined with Lapatinib on proliferation and apoptosis of triple negative breast cancer cells |
ZHU Jiyang1 CHEN Hua1 XU Yanfang1 SHAO Jinhui2 |
1.Department of Pharmacy, Hangzhou Lin′an Traditional Chinese Medicine Hospital, Zhejiang Province, Hangzhou 311300, China;
2.Department of Breast Surgery, Hangzhou Fuyang Traditional Chinese Medicine Hospital, Zhejiang Province, Hangzhou 311400, China |
|
|
Abstract Objective To investigate the effects of Berberine combined with Lapatinib on proliferation and apoptosis of MDA-MB-231 triple negative breast cancer cells. Methods MTT assay was used to detect the proliferation inhibition of single application for Berberine, Lapatinib and drug combination at different concentrations in MDA-MB-231 triple negative breast cancer cells. CompuSyn software was used to analyze the combined index CI of different dose groups and determine the best combined scheme. The cells were randomly divided into 4 groups: the blank control group, the Berberine group, the Lapatinib group and the drug combination group, and the optimal combination dose selected was used for drug intervention respectively. Flow cytometry was used to detect apoptosis in each group. Results Compared with the single drug, the combination of Berberine and Lapatinib inhibited the proliferation of MDA-MB-231 cells more significantly, and the difference was statistically significant (P < 0.05). CompuSyn software analysis results showed that the CI value of each combined dose was < 1, indicating that the two drugs had synergistic inhibitory effect. The dose group with the lowest CI value was selected for subsequent experiments. Compared with the the blank control group, the total apoptosis rate of the Berberine group and the Lapatinib group increased, and the differences were statistically significant (P < 0.05 or P < 0.01). Compared with the Berberine group and the Lapatinib group, the total apoptosis rate of the combined treatment group was increased, and the differences were statistically significant (P < 0.05). Conclusion Berberine combined with Lapatinib can enhance the ability of the proliferation inhibition and induce apoptosis of MDA-MB-231 triple negative breast cancer cells.
|
|
|
|
|
[1] Bianchini G,Balko JM,Mayer IA,et al. Triple-negative breast cancer:challenges and opportunities of a heterogeneous disease [J]. Nat Rev Clin Oncol,2016,13(11):674-690.
[2] 孙莉,赵毅.三阴性乳腺癌治疗的研究进展[J].现代肿瘤医学,2019,27(13):2420-2424.
[3] 尹海庆,苏莉,陈万贞,等.术后首发肺转移的三阴性乳腺癌临床病理特点及预后因素分析[J].现代肿瘤医学,2019,27(16):2872-2876.
[4] Wang Y,Zhang J,Ren S,et al. Branched-Chain Amino Acid Metabolic Reprogramming Orchestrates Drug Resistance to EGFR Tyrosine Kinase Inhibitors [J]. Cell Rep,2019,28(2):512-525.
[5] 覃咸雄,孙圣荣.CK5/6、EGFR和E-cadhenrin在三阴性乳腺癌中的表达及意义[J].解剖学研究,2018,40(3):169-173.
[6] Powles T,Huddart RA,Elliott T,et al. Phase Ⅲ,Double-Blind,Randomized Trial That Compared Maintenance Lapatinib Versus Placebo After First-Line Chemotherapy in Patients With Human Epidermal Growth Factor Receptor 1/2-Positive Metastatic Bladder Cancer [J]. J Clin Oncol,2017,35(1):48-55.
[7] Wang YL,Overstreet AM,Chen MS,et al. Combined inhibition of EGFR and c-ABL suppresses the growth of triple-negative breast cancer growth through inhibition of HOTAIR [J]. Oncotarget,2015,6(13):11150-11161.
[8] Lorenzen S,Riera Knorrenschild J,Haag GM,et al. Lapatinib versus lapatinib plus capecitabine as second-line treatment in human epidermal growth factor receptor 2-amplified metastatic gastro-oesophageal cancer:a randomised phase Ⅱ trial of the Arbeitsgemeinschaft Internistische Onkologie [J]. Eur J Cancer,2015,51(5):569-576.
[9] 唐劲奋.天然产物小檗胺增强伊马替尼治疗慢性粒细胞白血病的疗效及机制研究[D].杭州:浙江大学,2014.
[10] 郭子寒,杜琼,戴贤春,等.肿瘤分子靶向治疗药物的发展概况[J].上海医药,2018,39(5):5-9.
[11] Scharpenseel H,Hanssen A,Loges S,et al. EGFR and HER3 expression in circulating tumor cells and tumor tissue from non-small cell lung cancer patients [J]. Sci Rep,2019,9(1):7406.
[12] Adachi Y,Ohashi H,Imsumran A,et al. The effect of IGF-I receptor blockade for human esophageal squamous cell carcinoma and adenocarcinoma [J]. Tumor Boil,2014, 35(2):973-985.
[13] Elbaz M,Ahirwar D,Ravi J,et al. Novel role of cannabinoid receptor 2 in inhibiting EGF/EGFR and IGF-I/IGF-IR pathways in breast cancer [J]. Oncotarget,2017,8(18):29668-29678.
[14] Xu L,Qi Y,Xu Y,et al. Co-inhibition of EGFR and IGF1R synergistically impacts therapeutically on adrenocortical carcinoma [J]. Oncotarget,2016,7(24):36235-36246.
[15] 李赛赛.Lapatinib联合紫杉醇对食管癌的抗肿瘤活性及作用机制研究[D].新乡:新乡医学院,2018.
[16] Morrison CD,Allington TM,Thompson CL,et al. c-Abl inhibits breast cancer tumorigenesis through reactivation of p53-mediated p21 expression [J]. Oncotarget,2016,7(45):72777-72794.
[17] Fu R,Deng Q,Zhang H,et al. A novel autophagy inhibitor berbamine blocks SNARE-mediated autophagosome- lysosome fusion through upregulation of BNIP3 [J]. Cell Death Dis,2018,9(2):243.
[18] 吕雨晨,吴苗苗,房坤,等.地高辛对三阴性乳腺癌MDA-MB-231细胞凋亡作用的研究[J].中国医药导报,2019, 16(36):14-18,23.
[19] Jin X,Wu Y. Berbamine enhances the antineoplastic activity of gemcitabine in pancreatic cancer cells by activating transforming growth factor-beta/Smad signaling [J]. Anatomical record,2014,297(5):802-809.
[20] Zhang H,Jiao Y,Shi C,et al. Berbamine suppresses cell proliferation and promotes apoptosis in ovarian cancer partially via the inhibition of Wnt/β-catenin signaling [J]. Acta Biochim Biophys Sin(Shanghai),2018,50(6):532-539. |
|
|
|