Abstract
Vemurafenib has recently been used as drug for treatment of melanomas with BRAFV600E mutation. Unfortunately, treatment with only vemurafenib has not been sufficiently effective, with recurrence after a short period. In this study, three vemurafenib-resistant BRAFV600E melanoma cell lines, A375PR, A375MR and SKMEL-28R, were established from the original A375P, A375M and SKMEL-28 cell lines. Examination of the molecular mechanisms showed that the phosphorylation levels of MEK and ERK, which play key roles in the RAS/RAF/MEK/ERK signaling pathway, were reduced in these three cell lines, with increased phosphorylation levels of pAKTs limited to SKMEL-28R cells. Treatment of SKMEL-28R cells with 100 nM paclitaxel resulted in increased apoptosis and decreased cellular proliferation, invasion and colony formation via reduction of expression levels of EGFR and pAKTs. Moreover, vemurafenib-induced pAKTs in SKMEL-28R were decreased by treatment with an AKT inhibitor, MK-2206. Taken together, our results revealed that resistance mechanisms of BRAFV600E-mutation melanoma cells to vemurafenib depended on the cell type. Our results suggested that paclitaxel should be considered as a drug in combination with vemurafenib to treat melanoma cells.
| Original language | English |
|---|---|
| Pages (from-to) | 699-705 |
| Number of pages | 7 |
| Journal | Asian Pacific Journal of Cancer Prevention |
| Volume | 16 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2015 Jan 1 |
| Externally published | Yes |
Keywords
- AKT
- BRAFV600E
- EGFR
- Melanoma
- Paclitaxel
- Treatment resistance
- Vemurafenib
ASJC Scopus subject areas
- Epidemiology
- Oncology
- Public Health, Environmental and Occupational Health
- Cancer Research
Cite this
Treatment of vemurafenib-resistant SKMEL-28 melanoma cells with paclitaxel. / Thang, Nguyen Dinh; Nghia, Phan Tuan; Kumasaka, Mayuko Y.; Yajima, Ichiro; Kato, Masashi.
In: Asian Pacific Journal of Cancer Prevention, Vol. 16, No. 2, 01.01.2015, p. 699-705.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Treatment of vemurafenib-resistant SKMEL-28 melanoma cells with paclitaxel
AU - Thang, Nguyen Dinh
AU - Nghia, Phan Tuan
AU - Kumasaka, Mayuko Y.
AU - Yajima, Ichiro
AU - Kato, Masashi
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Vemurafenib has recently been used as drug for treatment of melanomas with BRAFV600E mutation. Unfortunately, treatment with only vemurafenib has not been sufficiently effective, with recurrence after a short period. In this study, three vemurafenib-resistant BRAFV600E melanoma cell lines, A375PR, A375MR and SKMEL-28R, were established from the original A375P, A375M and SKMEL-28 cell lines. Examination of the molecular mechanisms showed that the phosphorylation levels of MEK and ERK, which play key roles in the RAS/RAF/MEK/ERK signaling pathway, were reduced in these three cell lines, with increased phosphorylation levels of pAKTs limited to SKMEL-28R cells. Treatment of SKMEL-28R cells with 100 nM paclitaxel resulted in increased apoptosis and decreased cellular proliferation, invasion and colony formation via reduction of expression levels of EGFR and pAKTs. Moreover, vemurafenib-induced pAKTs in SKMEL-28R were decreased by treatment with an AKT inhibitor, MK-2206. Taken together, our results revealed that resistance mechanisms of BRAFV600E-mutation melanoma cells to vemurafenib depended on the cell type. Our results suggested that paclitaxel should be considered as a drug in combination with vemurafenib to treat melanoma cells.
AB - Vemurafenib has recently been used as drug for treatment of melanomas with BRAFV600E mutation. Unfortunately, treatment with only vemurafenib has not been sufficiently effective, with recurrence after a short period. In this study, three vemurafenib-resistant BRAFV600E melanoma cell lines, A375PR, A375MR and SKMEL-28R, were established from the original A375P, A375M and SKMEL-28 cell lines. Examination of the molecular mechanisms showed that the phosphorylation levels of MEK and ERK, which play key roles in the RAS/RAF/MEK/ERK signaling pathway, were reduced in these three cell lines, with increased phosphorylation levels of pAKTs limited to SKMEL-28R cells. Treatment of SKMEL-28R cells with 100 nM paclitaxel resulted in increased apoptosis and decreased cellular proliferation, invasion and colony formation via reduction of expression levels of EGFR and pAKTs. Moreover, vemurafenib-induced pAKTs in SKMEL-28R were decreased by treatment with an AKT inhibitor, MK-2206. Taken together, our results revealed that resistance mechanisms of BRAFV600E-mutation melanoma cells to vemurafenib depended on the cell type. Our results suggested that paclitaxel should be considered as a drug in combination with vemurafenib to treat melanoma cells.
KW - AKT
KW - BRAFV600E
KW - EGFR
KW - Melanoma
KW - Paclitaxel
KW - Treatment resistance
KW - Vemurafenib
UR - http://www.scopus.com/inward/record.url?scp=84925382483&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925382483&partnerID=8YFLogxK
U2 - 10.7314/APJCP.2015.16.2.699
DO - 10.7314/APJCP.2015.16.2.699
M3 - Article
VL - 16
SP - 699
EP - 705
JO - Asian Pacific Journal of Cancer Prevention
JF - Asian Pacific Journal of Cancer Prevention
SN - 1513-7368
IS - 2
ER -