Mechanism of Chinese medicine Fuzheng in reversing paclitaxel resistance in TLR4 over-expressed breast cancer
ZHANG Xiangjian1, ZHANG Xinxin2, MA Haiguang1, HU Xiaoqing1
1.Department of Oncology, Wenzhou Central Hospital, Wenzhou 325000, China; 2.Department of Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, China
ZHANG Xiangjian,ZHANG Xinxin,MA Haiguang, et al. Mechanism of Chinese medicine Fuzheng in reversing paclitaxel resistance in TLR4 over-expressed breast cancer[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2019, 49(11): 826-831.
Abstract:Objective: To investigate the mechanism of Fuzheng Chinese medicine combined with paclitaxel against TLR4 over-expressing breast cancer, and to confirm the sensitization effect of traditional Chinese medicine combined with chemotherapy for TLR4 over-expressed breast cancer MDA-MB-231 so as to select specific tumor phenotype for combination of traditional Chinese and western medicine. The target provides drug intervention to provide basic data. Methods: MTT assay was used to detect the proliferation inhibition effect of Fuzheng Chinese medicine, paclitaxel and two drugs on breast cancer cell lines T47D and MDA-MB-231. The apoptosis rate was detected by flow cytometry. Expression of the apoptosis related protein and TLR4/NF-kB signaling pathway-associated proteins was detected by Western blotting technology. Results: Fuzheng Chinese medicine and paclitaxel had synergistic effect in the treatment of MDA-MB-231 cell line; Fuzheng Chinese medicine assisted paclitaxel to induce apoptosis of MDA-MB-231 cell line (P<0.05); combined with Chinese medicine and paclitaxel, MDA-MB-231 Cell line TLR4/NF-kB signaling pathway was inhibited (P<0.05). Conclusion: In MDA-MB-231 cell line, Fuzheng Chinese medicine can increase cell apoptosis by inhibiting TLR4/NF-kB signaling pathway, thereby increasing the cell proliferation inhibition effect of paclitaxel on MDA-MB-231 breast cancer cell line and reversing paclitaxel-resistance in breast cancer.
[1] FAN L, STRASSER-WEIPPL K, LI J J, et al. Breast cancer in China[J]. Lancet Oncol, 2014, 15(7): e279-289.
[2] JIA L, LIN H, OPPENHEIM J, et al. US National Cancer Institute-China Collaborative Studies on Chinese Medicine and Cancer[J]. J Natl Cancer Inst Monogr, 2017, 2017(52): 58-61.
[3] MENG H, PENG N, YU M, et al. Treatment of triple-negative breast cancer with Chinese herbal medicine: A prospective cohort study protocol[J]. Medicine (Baltimore), 2017, 96(44): e8408.
[4] WANG X, FANG G, PANG Y. Chinese Medicines in the Treatment of Prostate Cancer: From Formulas to Extracts and Compounds[J]. Nutrients, 2018, 10(3): E283.
[5] LOU J S, YAO P, TSIM K W K. Cancer treatment by using traditional Chinese medicine: probing active compounds in anti-multidrug resistance during drug therapy[J]. Curr Med Chem, 2018, 25(38): 5128-5141.
[6] 韩飞, 幸仁汇, 陈琳琦, 等. 中药抗细菌耐药性的研究进展[J]. 中国中药杂志, 2016, 41(5): 813-817.
[7] HUANG B, ZHAO J, LI H, et al. Toll-like receptors on tumor cells facilitate evasion of immune surveillance[J]. Cancer Res, 2005, 65(12): 5009-5014.
[8] 吕宝军, 张红雨, 王晓鸿, 等. 乳腺癌组织TLR4蛋白表达及与细胞凋亡和增殖的关系[J]. 中华普通外科学文献(电子版), 2011, 5(3): 211-213.
[9] KELLY M G, ALVERO A B, CHEN R, et al. TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer[J]. Cancer Res, 2006, 66(7): 3859-3868.
[10] WU J, GUAN M, WONG P F, et al. Icariside II potentiates paclitaxel-induced apoptosis in human melanoma A375 cells by inhibiting TLR4 signaling pathway[J]. Food Chem Toxicol, 2012, 50(9): 3019-3024.
[11] RAJPUT S, VOLK-DRAPER L D, RAN S. TLR4 is a novel determinant of the response to paclitaxel in breast cancer[J].Mol Cancer Ther, 2013, 12(8): 1676-1687.
[12] TANIMURA N, SAITOH S, MATSUMOTO F, et al. Roles for LPS-dependent interaction and relocation of TLR4 and TRAM in TRIF-signaling[J]. Biochem Biophys Res Commun, 2008, 368(1): 94-99.
[13] 薛晓红, 江科, 李琼, 等. 乳腺癌患者治疗前后血清VEGF动态变化及乳癌术后方的干预作用[J]. 上海中医药杂志, 2011, 45(6): 46-48.
[14] 薛晓红, 刘胜, 杨新伟, 等. 乳宁冲剂及拆方对裸鼠移植瘤生长及肺转移的影响[J]. 上海中医药杂志, 2005, 39(7): 45-47.
[15] 阙华发, 陈红风, 高尚璞, 等. 乳宁II号防治乳腺癌MDA-MB-435裸鼠移植瘤生长转移作用及其抑制血管生成的机制研究[J]. 中国中医基础医学杂志, 2007, 13(8): 592-594.
[16] 刘玲琳, 刘胜. 乳移平配伍肺经引经药桔梗抗乳腺癌肺转移作用及机制的实验研究[J]. 上海中医药杂志, 2010, 44(10): 61-65.
[17] 姜华, 张艳, 王辰. 益气活血复方含药血清对人脐静脉内皮细胞TLR4及其下游髓样分化因子88、肿瘤坏死因子受体相关因子-6表达的影响[J]. 中国中西医结合杂志, 2010, 30(5): 519-522.
[18] 张彩霞, 江滨, 张亚杰, 等. 国内外文献对白术内酯Ⅱ抑制肿瘤细胞作用的浓度差异原因分析[J]. 中医药导报, 2017, 23(20): 30-32.
[19] ECKSTEIN-LUDWIG U, WEBB R J, VAN GOETHEM I D,
et al. Artemisinins target the SERCA of Plasmodium falci-parum[J]. Nature, 2003, 424(6951): 957-961.
[20] ARUMUGAM A, ABDULL RAZIS A F. Apoptosis as a mechanism of the cancer chemopreventive activity of glucosinolates: A review[J]. Asian Pac J Cancer Prev, 2018, 19(6): 1439-1448.