ABT-737 ameliorates docetaxel resistance in triple negative breast cancer cell line

Eunjoo Hwang; Seong-Hye Hwang; Jongjin Kim; Jin Hyun Park; Sohee Oh; Young A Kim; Ki-Tae Hwang

추천

검색

질문

자료유형: 학술저널

저자정보: Eunjoo Hwang (Seoul Metropolitan Government - Seoul National University Boramae Medical Center) Seong-Hye Hwang (Seoul Metropolitan Government - Seoul National University Boramae Medical Center) Jongjin Kim (Seoul Metropolitan Government - Seoul National University Boramae Medical Center) Jin Hyun Park (Seoul Metropolitan Government - Seoul National University Boramae Medical Center) Sohee Oh (Seoul Metropolitan Government - Seoul National University Boramae Medical Center) Young A Kim (Seoul Metropolitan Government - Seoul National University Boramae Medical Center) Ki-Tae Hwang (Seoul Metropolitan Government - Seoul National University Boramae Medical Center)

저널정보: 대한외과학회 Annals of Surgical Treatment and Research Annals of Surgical Treatment and Research Vol.95 No.5

발행연도: 2018.11

수록면: 240 - 248 (9page)

이용수

📌

연구주제

📖

연구배경

🔬

연구방법

🏆

연구결과

초록· 키워드

오류제보하기

Purpose: This study aimed to validate the synergistic effect of ABT-737 on docetaxel using MDA-MB-231, a triple negative breast cancer (TNBC) cell line overexpressing B-cell lymphoma-2 (Bcl-2).
Methods: Western blot analysis was performed to assess expression levels of Bcl-2 family proteins and caspase-related molecules. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle distribution was determined by flow cytometry analysis. Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (z-VAD-fmk) was used for pretreatment to assess the role of caspases.
Results: Cell viability of MDA-MB-231 after combination treatment with ABT-737 and docetaxel was significantly lower than that after docetaxel or ABT-737 monotherapy based on MTT assay (both P < 0.001), with a combination index of 0.41. The proportion of sub-G1 population after combination treatment was significantly higher than that after docetaxel or ABT-737 monotherapy (P = 0.001, P = 0.003, respectively). Pretreatment with z-VAD-fmk completely restored cell viability of MDA-MB-231 from apoptotic cell death induced by combination therapy (P = 0.001). Although pro-caspase-8 or Bid did not show significant change in expression level, pro-casepase-9 showed significantly decreased expression after combination treatment. Cleaved caspase-3 showed increased expression while poly (ADP-ribose) polymerase cleavage was induced after combination treatment. However, hypoxia-inducible factor 1-alpha and aldehyde dehydrogenase 1 totally lost their expression after combination treatment.
Conclusion: Combination of ABT-737 with docetaxel elicits synergistic therapeutic effect on MDA-MB-231, a TNBC cell line overexpressing Bcl-2, mainly by activating the intrinsic pathway of apoptosis. Therefore, adjunct of ABT-737 to docetaxel might be a new therapeutic option to overcome docetaxel resistance of TNBCs overexpressing Bcl-2.

#ABT-737 #Bcl-2 #Docetaxel #Drug resistance #Triple negative breast neoplasms

참고문헌 (30)

참고문헌 신청

[학술지(정기간행물)] - Foulkes WD / 2010 / Triple-negative breast cancer / N Engl J Med 363 : 1938 ~ 1948

[학술지(정기간행물)] - Carey L / 2010 / Triple-negative breast cancer:disease entity or title of convenience? / Nat Rev Clin Oncol 7 : 683 ~ 692

[학술지(정기간행물)] - Dent R / 2007 / Triplenegative breast cancer: clinical features and patterns of recurrence / Clin Cancer Res 13 (15 Pt 1) : 4429 ~ 4434

[학술지(정기간행물)] - Czabotar PE / 2014 / Control of apoptosis by the BCL-2 protein family : implications for physiology and therapy / Nat Rev Mol Cell Biol 15 : 49 ~ 63

[학술지(정기간행물)] - Tsujimoto Y / 1984 / Cloning of the chromosome breakpoint of neoplastic B cells with the t(14; 18)chromosome translocation / Science 226 : 1097 ~ 1099

함께 읽어보면 좋을 논문

논문 유사도에 따라 DBpia 가 추천하는 논문입니다. 함께 보면 좋을 연관 논문을 확인해보세요!