Zhou Wenchao, Cao Aili, Wang Li, Wu Dazheng
Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
Cell Biochem Biophys. 2015 May;72(1):241-9. doi: 10.1007/s12013-014-0444-0.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been identified as a promising anti-tumor agent against in a variety of cancers. However, gastric cancer cells are less sensitive than other cancer cells to TRAIL-induced apoptosis. Here, we combined TRAIL with kurarinone, a natural compound, to induce apoptosis in gastric cancer cell lines SGC7901. After the cells were treated with TRAIL and/or kurarinone, the cell viability and apoptosis were examined by MTT and flow cytometry, respectively. The expression of apoptosis-associated proteins was determined by western blot and q-RT-PCR. Kurarinone at low concentration significantly potentiated the cytotoxic effect of TRAIL by enhancing apoptosis as well as cell cycle arrest at G2/Mphase. The enhancement of apoptosis TRAIL induced by kurarinone involved downregulation of anti-apoptotic proteins Mcl-1 and c-FLIP as well as inhibition of STAT3 signaling. Moreover, we found that STAT3 inhibitor could synergistically enhanced TRAIL-induced apoptosis, similar to kurarinone. Kurarinone synergizes TRAIL-induced apoptosis in human gastric cancer cells. The synergistic effect between these two drugs is associated with downregulation of Mcl-1 and c-FLIP via inhibiting STAT3 signaling. The combination of TRAIL and kurarinone might be an effective regimen for the treatment of advanced gastric cancer.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）已被确定为一种有前景的针对多种癌症的抗肿瘤药物。然而，胃癌细胞对TRAIL诱导的凋亡比其他癌细胞更不敏感。在此，我们将TRAIL与一种天然化合物苦参酮联合使用，以诱导胃癌细胞系SGC7901发生凋亡。在用TRAIL和/或苦参酮处理细胞后，分别通过MTT法和流式细胞术检测细胞活力和凋亡情况。通过蛋白质免疫印迹法和定量逆转录聚合酶链反应测定凋亡相关蛋白的表达。低浓度的苦参酮通过增强凋亡以及使细胞周期阻滞在G2/M期，显著增强了TRAIL的细胞毒性作用。苦参酮诱导TRAIL凋亡的增强涉及抗凋亡蛋白Mcl-1和c-FLIP的下调以及STAT3信号通路的抑制。此外，我们发现STAT3抑制剂可协同增强TRAIL诱导的凋亡，类似于苦参酮。苦参酮协同TRAIL诱导人胃癌细胞凋亡。这两种药物之间的协同作用与通过抑制STAT3信号通路下调Mcl-1和c-FLIP有关。TRAIL与苦参酮的联合可能是治疗晚期胃癌的有效方案。
