Details

Autor(en) / Beteiligte

• Son, Kyoung-Hwa
• Kim, Min-Young
• Shin, Jung-Young
• Kim, Jeong-Oh
• Kang, Jin-Hyoung

Titel

Synergistic Antitumor Effect of Taxanes and CDK4/6 Inhibitor in Lung Cancer Cells and Mice Harboring KRAS Mutations

Ist Teil von

• Anticancer research, 2021-10, Vol.41 (10), p.4807-4820

Ort / Verlag

Athens: International Institute of Anticancer Research

Erscheinungsjahr

2021

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.