Abstract 5563: Tripterygium induces apoptosis in NSCLC via mitochondria dysfunction

Abstract

Abstract Lung cancer remains the leading cause of cancer deaths globally. Patients with non-small cell lung cancer (NSCLC) account for 80% of all lung cancer cases. Active mutation of EGFR was identified as one of the key anti-cancer target for NSCLC patients. Recently, tyrosine kinase inhibitor, like gefitinib which can specifically inhibit the activation of EGFR, emerges as a new potential anticancer drug. However, drug resistance remains an unsolved problem. Most of patient acquired resistance to this inhibitor within 12 months. Therefore, it is necessary and urgent to discover more effective potential agents as candidate drugs for treating gefitinib resistant NSCLC. Tripterygium, a triterpene extracted from the Chinese herb “Thunder of God Vine”, has been shown to have multiple bioactivities. Its anti-cancer effect has been proved in many kinds of cancers. However, the effect of Tripterygium on gefitinib-resistant NSCLC cells is still unknown. In this study, we examined the potency of Tripterygium in induction of apoptosis in a gefitinib-resistant NSCLC cell line and explored its underlying anti-cancer mechanism. Our results demonstrated that Tripterygium induced its apoptotic effect on NSCLC cells in a dose- and time-dependent manner. Moreover, the function of mitochondria was disrupted by the treatment of Tripterygium. The mitochondria membrane potential was gradually loss, and the ratio of Bax/Bcl-2 which is the indicator of mitochondria membrane integrity, was significantly up-regulated after the treatment of Tripterygium. Although the caspases were activated, the treatment of pan-caspase inhibitor could only partially inhibit the level of apoptosis. Moreover, the level of Hsp90 client proteins, EGFR and its downstream target AKT, were measured. Interestingly, both of them were remarkably decreased after Tripterygium treatment. Taken together, our data suggest that Tripterygium, which may be developed as a promising agent for gefitinib-resistant NSCLC patient, induced apoptosis through mitochondria dysfunction and EGFR degradation in gefitinib-resistant NSCLC cells. Citation Format: Xing-Xing Fan, Na Li, Jin-Lin Wu, Yan-Ling Zhou, Liang Liu, Jian-Xing He, Elaine L. Leung. Tripterygium induces apoptosis in NSCLC via mitochondria dysfunction. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5563. doi:10.1158/1538-7445.AM2015-5563