AI Article Synopsis
- LY2835219 (LY) is a CDK4/6 inhibitor that halts cell growth by causing G1 arrest, while docetaxel (DTX) and paclitaxel (PTX) are chemotherapeutic agents that induce cell death through G2/M arrest.
- The study found that the combination of DTX followed by LY displayed a stronger anticancer effect than using DTX or LY alone, and this effect was consistent in both KRAS mutated and non-mutated lung adenocarcinoma cells and mice.
- The research concluded that using DTX before LY significantly enhances apoptosis and disrupts the cell cycle in cancer cells, suggesting a potential new treatment strategy for lung cancer.
Article Abstract
Background/aim: LY2835219 (LY), a novel CDK4/6 inhibitor, prevents cell proliferation through G1 arrest. Docetaxel (DTX) and paclitaxel (PTX) are cytotoxic drugs targeting tubulin-mediated apoptotic cell death via G2/M arrest. We evaluated the antitumor effects of DTX/PTX and LY individually and in combination in lung adenocarcinoma cells with or without KRAS mutations and xenograft mice harboring KRAS mutations.
Materials And Methods: We investigated in vitro/in vivo changes in signaling molecules and analyzed cell proliferation, cycle, and apoptosis via flow cytometry and western blotting.
Results: LY cytotoxicity was dose-dependent and varied with KRAS mutation status. DTX→LY showed synergistic cytotoxicity regardless of KRAS mutation. Furthermore, the synergistic effect of PTX→LY was significantly greater than that of PTX+LY. DTX→LY remarkably reduced the number of G0/G1 cells and increased the number of G2/M arrested cells, resulting in an increase in apoptosis and subG1 cells.
Conclusion: DTX→LY has synergistic antitumor effect in lung cancer cells and xenograft mice regardless of KRAS mutation.
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| http://dx.doi.org/10.21873/anticanres.15296 | DOI Listing |
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