caa a22 4500 606236058 CHVBK 20210128101245.0 cr unu---uuuuu 210128e20150801xx s 000 0 eng 10.1007/s11010-015-2423-1 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2423-1 Low inducible expression of p21Cip1 confers resistance to paclitaxel in BRAF mutant melanoma cells with acquired resistance to BRAF inhibitor [Elektronische Daten] [Gun-Hee Jang, Na-Yeon Kim, Michael Lee] The therapeutic efficacy of oncogenic BRAF inhibitor is limited by the onset of acquired resistance. In this study, we investigated the potential therapeutic effects of the mitotic inhibitor paclitaxel on three melanoma cell lines with differing sensitivity to the BRAF inhibitor. Of the two BRAF inhibitor-resistant cell lines, A375P/Mdr cells harboring the BRAF V600E mutant were resistant and the wild-type BRAF SK-MEL-2 cells were sensitive to paclitaxel. In particular, paclitaxel caused the growth inhibition of SK-MEL-2 cells to a much greater extent than it caused growth inhibition of A375P cells. Paclitaxel exhibited no significant effect on the phosphorylation of MEK-ERK in any cell lines tested, regardless of both the BRAF mutation and the drug resistance, implying that paclitaxel activity is independent of MEK-ERK inhibition. In A375P cells, paclitaxel treatment resulted in a marked emergence of apoptotic cells after mitotic arrest, concomitant with a remarkable induction of p21Cip1. However, paclitaxel only moderately increased the levels of p21Cip1 in A375P/Mdr cells, which exhibited a strong resistance to paclitaxel. The p21Cip1 overexpression partially conferred paclitaxel sensitivity to A375P/Mdr cells. Interestingly, we found an extremely low background expression level of p21Cip1 in SK-MEL-2 cells lacking normal p53 function, which caused much greater G2/M arrest than that seen in A375P cells. Taken together, these results suggest that paclitaxel may be an effective anticancer agent through regulating the expression of p21Cip1 for the treatment of BRAF mutant melanoma cells resistant to BRAF inhibitors. Springer Science+Business Media New York, 2015 Paclitaxel nationallicence BRAF inhibitor-resistance nationallicence Melanoma nationallicence Mitotic arrest nationallicence p21Cip1 nationallicence Apoptosis nationallicence Jang Gun-Hee Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, 406-772, Incheon, Republic of Korea aut Kim Na-Yeon Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, 406-772, Incheon, Republic of Korea aut Lee Michael Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, 406-772, Incheon, Republic of Korea aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 406/1-2(2015-08-01), 53-62 0300-8177 406:1-2<53 2015 406 11010 https://doi.org/10.1007/s11010-015-2423-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2423-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Jang Gun-Hee Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, 406-772, Incheon, Republic of Korea aut NATIONALLICENCE 700 1- Kim Na-Yeon Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, 406-772, Incheon, Republic of Korea aut NATIONALLICENCE 700 1- Lee Michael Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, 119 Academy-ro, Yeonsu-gu, 406-772, Incheon, Republic of Korea aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 406/1-2(2015-08-01), 53-62 0300-8177 406:1-2<53 2015 406 11010