Synergistic antitumor effect of taxanes and CDK4/6 Inhibitor in lung cancer cells and mice harboring KRAS mutations

Kyoung Hwa Son; Min Young Kim; Jung Young Shin; Jeong Oh Kim; Jin Hyoung Kang

doi:10.21873/anticanres.15296

Synergistic antitumor effect of taxanes and CDK4/6 Inhibitor in lung cancer cells and mice harboring KRAS mutations

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

Daegu Catholic University School of Medicine

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English
Pages (from-to)	4807-4820
Number of pages	14
Journal	Anticancer Research
Volume	41
Issue number	10
DOIs	https://doi.org/10.21873/anticanres.15296
State	Published - Oct 2021

Bibliographical note

Funding Information:
None of the Authors have received financial support from the sponsor. The Authors declare no conflicts of interest in association with the present study.

Publisher Copyright:
© 2021 International Institute of Anticancer Research. All rights reserved.

Keywords

CDK4/6 inhibitor
Docetaxel
KRAS mutation
Lung cancer
Paclitaxel
Synergism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.21873/anticanres.15296

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title = "Synergistic antitumor effect of taxanes and CDK4/6 Inhibitor in lung cancer cells and mice harboring KRAS mutations",

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.",

keywords = "CDK4/6 inhibitor, Docetaxel, KRAS mutation, Lung cancer, Paclitaxel, Synergism",

author = "Son, {Kyoung Hwa} and Kim, {Min Young} and Shin, {Jung Young} and Kim, {Jeong Oh} and Kang, {Jin Hyoung}",

note = "Funding Information: None of the Authors have received financial support from the sponsor. The Authors declare no conflicts of interest in association with the present study. Publisher Copyright: {\textcopyright} 2021 International Institute of Anticancer Research. All rights reserved.",

year = "2021",

month = oct,

doi = "10.21873/anticanres.15296",

language = "English",

volume = "41",

pages = "4807--4820",

journal = "Anticancer Research",

issn = "0250-7005",

publisher = "International Institute of Anticancer Research",

number = "10",

}

TY - JOUR

T1 - Synergistic antitumor effect of taxanes and CDK4/6 Inhibitor in lung cancer cells and mice harboring KRAS mutations

AU - Son, Kyoung Hwa

AU - Kim, Min Young

AU - Shin, Jung Young

AU - Kim, Jeong Oh

AU - Kang, Jin Hyoung

N1 - Funding Information: None of the Authors have received financial support from the sponsor. The Authors declare no conflicts of interest in association with the present study. Publisher Copyright: © 2021 International Institute of Anticancer Research. All rights reserved.

PY - 2021/10

Y1 - 2021/10

N2 - 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.

AB - 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.

KW - CDK4/6 inhibitor

KW - Docetaxel

KW - KRAS mutation

KW - Lung cancer

KW - Paclitaxel

KW - Synergism

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SN - 0250-7005

VL - 41

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JO - Anticancer Research

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Synergistic antitumor effect of taxanes and CDK4/6 Inhibitor in lung cancer cells and mice harboring KRAS mutations

Abstract

Bibliographical note

Keywords

UN SDGs

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