Preclinical evaluation and reverse phase protein Array-based profiling of PI3K and MEK inhibitors in endometrial carcinoma in vitro

Table 1 IC₅₀s of endometrial cancer cell lines (n = 13) to the PI3Ki pictilisib, PI3K/mTORi apitolisib and the MEKi cobimetinib as single agents (n = 13), and the combination of pictilisib with cobimetinib and apitolisib with cobimetinib (n = 11)

Cell Line	Mutational status	PTEN expression	PI3Ki Pictilisib (uM)	PI3K/mTORi Apitolisib (uM)	MEKi Cobimetinib (uM)	Combination of Pictilisib:Cobimetinib (uM)		Combination of Apitolisib:Cobimetinib (uM)
Cell Line	Mutational status	PTEN expression	IC₅₀	IC₅₀	IC₅₀	IC₅₀	CI at ED₇₅	IC50	CI at ED₇₅
SKUT2	PIK3CA only	High	0.413	0.196	0.101	0.096	0.138	0.049	0.152
MFE280	PIK3CA only	High	0.440	0.247	0.461	0.207	0.357	0.091	0.528
EN1078D	PTEN + PIK3R1	High	0.242	0.079	0.178	0.103	0.634	0.057	0.468
MFE296	PTEN + PIK3CA	High	0.273	0.106	0.301	0.383	1.037	0.120	0.650
ETN1	PTEN	High	0.544	0.387	1.077	0.174	0.426	0.177	0.495
AN3CA	PTEN + PIK3R1	Low	0.057	0.028	0.518	0.339	0.129	0.070	0.142
HEC59	PTEN + PIK3R1	Low	0.189	0.018	3.289	–	–	–	–
EN	PTEN + PIK3CA + PIK3R1	Low	1.597	0.548	36.511	3.117	1.555	2.175	1.200
HEC1A	KRAS + PIK3CA	High	2.054	0.214	0.012	–	–	–	–
HEC1B	KRAS + PIK3CA	High	0.798	0.704	0.033	0.050	0.031	0.054	0.035
HEC50	KRAS + PIK3R1	High	0.247	0.210	0.001	0.131	4.921	0.169	6.613
EFE184	WT for all	High	0.372	0.368	0.149	0.074	0.433	0.157	0.328
KLE	WT for all	High	2.796	7.253	39.337	0.644	0.142	0.144	0.005

Drug combinations exhibiting antagonistic effects (CI values > 1) are in shown bold
IC₅₀ inhibitor concentration to inhibit 50% of the cell growth, PI3Ki PI3K inhibitor, PI3K/mTORi PI3K/mTOR inhibitor, MEKi MEK inhibitor, CI Combination Index, ED₇₅ Effective Dose exhibiting 75% of loss in cell viability

ISSN: 1471-2407