Pan Yue, Zhang Yunqiu, Chen Qing, Tao Xufeng, Liu Jianzhou, Xiao Gary Guishan
School of Chemical Engineering, Dalian University of Technology, Dalian, China.
Functional Genomics and Proteomics Laboratory, Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, United States.
Front Pharmacol. 2019 Jul 26;10:843. doi: 10.3389/fphar.2019.00843. eCollection 2019.
Metabolic reprogramming is thought to be one of the initiators in cancer drug resistance. It has been shown that CTAB is capable of interfering the efficiency of cancer therapy by regulation of cell metabolic reprogramming. In this study, we hypothesized that AMPK as a key metabolic regulator plays a crucial role in regulation of breast cancer drug resistance, which could be alleviated by treatment of CTAB. We observed that CTAB can improve the DOX sensitivity of the breast cancer cells by inhibition of the ATP-dependent drug-efflux pump P-gp complex through activation of the AMPK-HIF-1α-P-gp cascades. The CTAB effect was also confirmed showing low systemic toxicity. Taken together, our results showed that CTAB sensitized drug resistance of breast cancer to DOX chemotherapy by activating AMPK signaling cascades both and , suggested that CTAB may be developed as a promising and novel chemosensitizer and chemotherapeutic candidate for breast cancer treatment.
代谢重编程被认为是癌症耐药性的引发因素之一。研究表明，十六烷基三甲基溴化铵（CTAB）能够通过调节细胞代谢重编程来干扰癌症治疗的效果。在本研究中，我们假设作为关键代谢调节因子的腺苷酸活化蛋白激酶（AMPK）在乳腺癌耐药性调节中起关键作用，而CTAB治疗可缓解这种耐药性。我们观察到，CTAB可通过激活AMPK - 低氧诱导因子-1α（HIF-1α）- P-糖蛋白（P-gp）级联反应，抑制ATP依赖的药物外排泵P-gp复合物，从而提高乳腺癌细胞对阿霉素（DOX）的敏感性。CTAB的效果也得到了证实，且显示出低全身毒性。综上所述，我们的结果表明，CTAB通过激活AMPK信号级联反应使乳腺癌对DOX化疗的耐药性敏感化，这表明CTAB可能被开发成为一种有前景的新型化学增敏剂和乳腺癌治疗的化疗候选药物。
