Combination therapy with vemurafenib (PLX4032/RG7204) and metformin in melanoma cell lines with distinct driver mutations

Table 2 BRAF^V600E and BRAF^WT cell lines used for detailed analysis.

Cell Line	BRAF/NRAS	Cell line characteristics
M249	BRAF^V600E	Single agent vemurafenib: Highly sensitive Single agent metformin: Highly sensitive Combination: Slight synergy
M249-AR4	BRAF^V600E NRAS^Q61K	Single agent vemurafenib: Resistant Single agent metformin: Intermediate sensitive Combination: Antagonistic
M263	BRAF^V600E	Single agent vemurafenib: Resistant Single agent metformin: Intermediate sensitive Combination: Slight synergy
M308	BRAF^V600E	Single agent vemurafenib: Resistant Single agent metformin: Highly sensitive Combination: Antagonistic
SKMEL28	BRAF^V600E	Single agent vemurafenib: Intermediate sensitive Single agent metformin: Resistant Combination: Antagonistic
M207	NRAS^Q61L	Single agent vemurafenib: Resistant Single agent metformin: Resistant Combination: Slight synergy
M296	NRAS^Q61L	Single agent vemurafenib: Resistant Single agent metformin: Highly sensitive Combination: Slight synergy
SKMEL173	NRAS^Q61K	Single agent vemurafenib: Resistant Single agent metformin: Resistant Combination: Highly antagonistic
WM1366	NRAS	Single agent vemurafenib: Resistant Single agent metformin: Highly sensitive Combination: Slight synergy
M257	Wild type	Single agent vemurafenib: Resistant Single agent metformin: Intermediate sensitive Combination: Slight synergy

Legend: Sensitivity to single agent vemurafenib: highly sensitive if IC50 < 1 μM; intermediate sensitive with IC50 1-10 μM; resistant if IC50 > 10 μM. Sensitivity to single agent metformin: highly sensitive if IC50 < 10 mM; intermediate sensitive with IC50 10-20 mM; resistant if IC50 > 20 mM. Sensitivity to the combination of vemurafenib and metformin: CI > 1 antagonistic; CI 1-0.3 slight synergy; CI < 0.3 strong synergy.