Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Biliary-Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Toxicol In Vitro. 2019 Feb;54:345-353. doi: 10.1016/j.tiv.2018.10.019. Epub 2018 Oct 31.
In contrast to the steady increase in survival observed for most cancer types, advances have been slow for pancreatic cancers. Current chemotherapy has limited benefits for patients with pancreatic cancer. Therefore, there is an urgent need for effective pancreatic cancer treatment strategies. At present, targeting the autophagic pathway is regarded as a promising new strategy for cancer treatment. Danthron (1,8-dihydroxyanthrquinone), a component from Rheum palmatum L. (polygonaceae), has several biological activities. However, the inhibition of autophagy by danthron has never been recognized, previously.Here we find that danthron may prevent autophagy, inhibit proliferation and induce apoptosis in pancreatic cancer cells in vitro. Autophagy induced by doxorubicin plays a protective role in pancreatic cancer cells and inhibition of autophagy by chloroquine or silencing autophagy protein 5 (Atg5) may chemosensitize pancreatic cancer cell lines to doxorubicin. Similarly, inhibition of autophagy by danthron also enhances toxicity of doxorubicin to pancreatic cancer cells. These results indicate that danthron has an anticancer effect and can sensitize the chemotherapeutic effect of doxorubicin on pancreatic cancer cells. These findings also suggest that inhibition of autophagy may be an effective way to promote the chemotherapy of pancreatic cancer.
与大多数癌症类型的生存率稳步提高形成对比的是，胰腺癌的进展缓慢。目前的化疗对胰腺癌患者的益处有限。因此，迫切需要有效的胰腺癌治疗策略。目前，靶向自噬途径被认为是癌症治疗的一种有前途的新策略。大黄素（1,8-二羟基蒽醌）是大黄（蓼科）的一种成分，具有多种生物学活性。然而，大黄素抑制自噬以前从未被认识到。在这里，我们发现大黄素可能在体外预防自噬、抑制胰腺癌细胞增殖并诱导细胞凋亡。阿霉素诱导的自噬在胰腺癌细胞中起保护作用，氯喹或沉默自噬蛋白 5（Atg5）抑制自噬可使胰腺癌细胞系对阿霉素增敏。同样，大黄素抑制自噬也增强了阿霉素对胰腺癌细胞的毒性。这些结果表明，大黄素有抗癌作用，并能增强阿霉素对胰腺癌细胞的化疗效果。这些发现还表明，抑制自噬可能是促进胰腺癌化疗的有效途径。
