Abstract 2183: Baicalein and meformin decrease small cell lung cancer growth by inhibiting the mTOR pathway in itro

Abstract

Abstract Background: Metformin use has been associated with decreased lung cancer risk in several observational studies and is currently in clinical trial in conjunction with standard chemotherapeutics. One possible antitumor mechanism is the negative regulation of the mTOR pathway. We previously reported that the natural product Baicalein has antitumor effects through targeting mTOR pathway. We hypothesized that Baicalein to have antitumor effects in small cell lung cancer. Methods: H1417 small cell lung cancer cells were cultured and treated with increasing doses of Baicalein or Metformin. The cells were harvested at 24 hours and subjected to Western blotting staining for the downstream products of the mTOR pathway. Cell proliferation was determined by MTT assay at 24, 48, and 72 hours. MTT conversion to formazan dye correlates with the number of living cells. Results: We found a dose dependent decrease in the downstream mTOR1 targets pS6K1 and pS6 using both Baicalein and Metformin. There was also an increase in the expression of the mTOR inhibitors DDIT4 and IRF-1. Using the MTT assay, we were able to demonstrate a marked dose dependent decrease in cell proliferation that was sustained over 72 hours from treatment. Interestingly, Baicalein has a markedly higher potency working at micromolar doses verses Metformin which required millimolar doses. Conclusions: Both Baicalein and Metformin effectively decrease cell proliferation in small cell lung cancer cells in vitro. We have shown these drugs to target the mTOR pathway. Cell proliferation is inhibited at a markedly smaller dose by Baicalein compared with Metformin. Baicalein may be useful in cancer chemotherapy and chemoprevention. Citation Format: Emily F. Marcinkowski, Dan Raz, Bing Shen, Quanhua Xing, Jin Yan, Wei Wen, Ernest Han, John Yim. Baicalein and meformin decrease small cell lung cancer growth by inhibiting the mTOR pathway in itro. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2183.