Abstract 5110: The role triptolide in sensitizing lung tumor cells to cisplatin-induced apoptosis

Cisplatin is an anticancer drug used in treatment for many types of cancer, including lung cancer. The quick development of tumor cell drug resistance, however, greatly hindered the effectiveness of cisplatin in cancer treatment. Exploring new strategies that can sensitize tumor cells to cisplatin treatment, therefore, is essential for improving the effectiveness of cisplatin in cancer treatment. Triptolide is a bioactive ingredient isolated from Tripterygium wilfordii, a traditional Chinese herbal medicine that has been used to treat immune-related disorders. Recent studies revealed that Triptolide possesses potent antitumor properties through CDK7-depedent RNA polymerase II (Pol II) degradation and global transcription inhibition by binding to the XPB subunit of general transcription factor TFIIH and inhibiting its ATPase activity. We have studied the possibility of using Triptolide to sensitize lung tumor cell to cisplatin-induced apoptosis. Using both HTB182 and CRL5985 lung tumor cells, our caspase 3 activation studies demonstrated that the presence of low-level Triptolide greatly sensitized these lung tumor cells to cisplatin-induced apoptosis. Our western blots results indicated that the presence of low-level Triptolide increased the cisplatin-induced expression of PUMA but reduced expression of Bcl-XL in these lung tumor cells. Our immune-blotting studies revealed that the RNA Pol II level was not significantly affected by the presence of low-level Triptolide. Our real time PCR studies results indicated that expression levels of several tested genes also were not affected by the presence of Triptolide. These results suggest that the presence of low levels of triptolide sensitizes the lung cancer cells to cisplatin-induced apoptosis through binding to XPB of the TFIIH and inhibiting the DNA repair activity for cisplatin DNA damage, resulting in increased apoptosis of the lung tumor cells. Therefore, the presence of low levels of triptolide sensitizes lung tumor cells to cisplatin-induced apoptosis. Citation Format: Gan Wang, Xiaoxin Susan Xu, Yi Zhang. The role triptolide in sensitizing lung tumor cells to cisplatin-induced apoptosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5110. doi:10.1158/1538-7445.AM2014-5110