Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma
Plumbagin Enhances the Anticancer Efficacy of Cisplatin by Increasing Intracellular ROS in Human Tongue Squamous Cell Carcinoma
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白花丹素通过增加人舌鳞状细胞癌细胞内ROS来增强顺铂的抗癌功效
DOI：
10.1155/2020/5649174
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发表时间：
2020-03-26
影响因子：
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通讯作者：
Qiu, Jiaxuan
中科院分区：
文献类型：
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作者：
Xue, Danfeng;Pan, Shu-Ting;Qiu, Jiaxuan
顺铂广泛应用于舌鳞癌的治疗，但其耐药性和毒副作用限制了其临床疗效。因此，迫切需要一种能够增强顺铂的抗癌效果同时降低副作用的新型化合物。我们以前已经表明，白花丹素（PLB），一种抗癌植物化学物质，能够抑制TSCC在体外和体内的生长。本研究旨在探讨PLB逆转TSCC对顺铂耐药的作用及其分子机制。在此，我们发现PLB增强了CAL 27和顺铂耐药CAL 27/CDDP细胞中顺铂诱导的细胞毒性、凋亡和自噬。PLB可通过增加细胞内活性氧（ROS）的产生抑制TSCC细胞的生长和存活。此外，PLB和顺铂的联合治疗通过增加细胞内ROS导致TSCC活力、凋亡和自噬的协同抑制，这可能是通过激活JNK和抑制AKT/mTOR信号通路实现的。最后，还在体内证明了协同治疗。因此，PLB联合顺铂是治疗TSCC顺铂耐药的潜在治疗策略。
Cisplatin is widely used in the treatment of tongue squamous cell carcinoma (TSCC), but its clinical efficacy is limited by drug resistance and toxic side effects. Hence, a novel compound capable of enhancing the anticancer effect of cisplatin while reducing the side effects is urgently needed. We have previously shown that plumbagin (PLB), an anticancer phytochemical, is able to inhibit the growth of TSCC in vitro and in vivo. The objective of this study was to investigate the effect of PLB in reversing the resistance of TSCC to cisplatin as well as its molecular mechanisms. Here, we found that PLB enhances cisplatin-induced cytotoxicity, apoptosis, and autophagy in CAL27 and cisplatin-resistant CAL27/CDDP cells. PLB could inhibit the viability and growth of TSCC cells by increasing the production of intracellular reactive oxygen species (ROS). In addition, the combination treatment of PLB and cisplatin resulted in a synergistic inhibition of TSCC viability, apoptosis, and autophagy by increasing intracellular ROS, which may be achieved by activating JNK and inhibiting AKT/mTOR signaling pathways. Finally, the synergistic treatment was also demonstrated in vivo. Therefore, PLB combined with cisplatin is a potential therapeutic strategy against therapy TSCC cisplatin resistance.