Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions
Yıl: 2021 Cilt: 36 Sayı: 1 Sayfa Aralığı: 8 - 16 Metin Dili: İngilizce DOI: 10.5505/tjo.2020.2380 İndeks Tarihi: 17-05-2022
Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions
Öz: OBJECTIVE Defects in apoptotic cell death which restrict the success of conventional cytotoxic therapies have pivotal roles in a number of pathological conditions including cancer. However, a novel drug class targeting pro-survival Bcl-2 protein family members has been developed with the understanding of the structures and interactions of Bcl-2 proteins. Within this new class, Bcl-2/Bcl-xL inhibitor Navitoclax and Bcl-2 specific inhibitor Venetoclax have been shown to demonstrate strong anticancer activities on several types of cancers. But their low affinity to other anti-apoptotic proteins limits their clinical usage. Here, we investigated the cytotoxic and apoptotic effects of Navitoclax/Venetoclax and their combinations with specific tyrosine kinase inhibitor Apatinib on estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cell lines. METHODS MTT assay was used for the evaluation of the inhibition of cancer cell proliferation. ELISA test and Quantitative real-time PCR assay was performed to determine the role of caspase-3, Bak, Bax, Bcl-2, Bcl-xL and Mcl-1 proteins in the inhibition of cell proliferation triggered by the tested agents. RESULTS We found that aggressive MDA-MB-231 cell line was more sensitive to all tested agents. Apatinib significantly enhanced Navitoclax/Venetoclax mediated inhibition of cell viability in both cancer cell lines despite up-regulation in the expression levels of Bcl-2 and Mcl-1 genes. We further demonstrated significant Bak/Bax and caspase-3 expression in less aggressive MCF-7 cells. CONCLUSION Our findings have impacts on Navitoclax/Venetoclax plus Apatinib based therapy for breast adenocarcinoma. On the other hand, further studies should be conducted to elucidate the mechanisms underlying synergistic effects of Navitoclax/Venetoclax plus Apatinib combinations.
Anahtar Kelime: Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
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| APA | Kavakcıoğlu Yardımcı B, OZGUN ACAR O, semiz a, SEN A (2021). Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions . , 8 - 16. 10.5505/tjo.2020.2380 |
| Chicago | Kavakcıoğlu Yardımcı Berna,OZGUN ACAR Ozden,semiz asli,SEN Alaattin Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions . (2021): 8 - 16. 10.5505/tjo.2020.2380 |
| MLA | Kavakcıoğlu Yardımcı Berna,OZGUN ACAR Ozden,semiz asli,SEN Alaattin Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions . , 2021, ss.8 - 16. 10.5505/tjo.2020.2380 |
| AMA | Kavakcıoğlu Yardımcı B,OZGUN ACAR O,semiz a,SEN A Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions . . 2021; 8 - 16. 10.5505/tjo.2020.2380 |
| Vancouver | Kavakcıoğlu Yardımcı B,OZGUN ACAR O,semiz a,SEN A Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions . . 2021; 8 - 16. 10.5505/tjo.2020.2380 |
| IEEE | Kavakcıoğlu Yardımcı B,OZGUN ACAR O,semiz a,SEN A "Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions ." , ss.8 - 16, 2021. 10.5505/tjo.2020.2380 |
| ISNAD | Kavakcıoğlu Yardımcı, Berna vd. "Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions ". (2021), 8-16. https://doi.org/10.5505/tjo.2020.2380 |
| APA | Kavakcıoğlu Yardımcı B, OZGUN ACAR O, semiz a, SEN A (2021). Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions . Türk Onkoloji Dergisi, 36(1), 8 - 16. 10.5505/tjo.2020.2380 |
| Chicago | Kavakcıoğlu Yardımcı Berna,OZGUN ACAR Ozden,semiz asli,SEN Alaattin Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions . Türk Onkoloji Dergisi 36, no.1 (2021): 8 - 16. 10.5505/tjo.2020.2380 |
| MLA | Kavakcıoğlu Yardımcı Berna,OZGUN ACAR Ozden,semiz asli,SEN Alaattin Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions . Türk Onkoloji Dergisi, vol.36, no.1, 2021, ss.8 - 16. 10.5505/tjo.2020.2380 |
| AMA | Kavakcıoğlu Yardımcı B,OZGUN ACAR O,semiz a,SEN A Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions . Türk Onkoloji Dergisi. 2021; 36(1): 8 - 16. 10.5505/tjo.2020.2380 |
| Vancouver | Kavakcıoğlu Yardımcı B,OZGUN ACAR O,semiz a,SEN A Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions . Türk Onkoloji Dergisi. 2021; 36(1): 8 - 16. 10.5505/tjo.2020.2380 |
| IEEE | Kavakcıoğlu Yardımcı B,OZGUN ACAR O,semiz a,SEN A "Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions ." Türk Onkoloji Dergisi, 36, ss.8 - 16, 2021. 10.5505/tjo.2020.2380 |
| ISNAD | Kavakcıoğlu Yardımcı, Berna vd. "Apatinib Sensitizes Human Breast Cancer Cells against Navitoclax and Venetoclax Despite Up-regulated Bcl-2 and Mcl-1 Gene Expressions ". Türk Onkoloji Dergisi 36/1 (2021), 8-16. https://doi.org/10.5505/tjo.2020.2380 |
