3D Growth of Cancer Cells Elicits Sensitivity to Kinase Inhibitors but Not Lipid Metabolism Modifiers

doi:10.1158/1535-7163.MCT-17-0857

PMC full text:

Mol Cancer Ther. Author manuscript; available in PMC 2019 Jul 5.

Published in final edited form as:

Mol Cancer Ther. 2019 Feb; 18(2): 376–388.

Published online 2018 Nov 26. doi: 10.1158/1535-7163.MCT-17-0857

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Table 2.

Growth inhibition of PC3 and MDA-MB-468 cells in 2D and 3Dgrowth following treatment with inhibitors against metabolic enzymes PDHK, ACC, FASN, and DGAT, and kinases PI3K, AKT, and mTOR

		Prostate cancer (PC3)		Breast cancer (MDA-MB-468)
Type	Enzyme target	2D	3D	2D	3D
Metabolic targets	FASN	N = 26 μmol/L	7.2 μmol/L	N = 19 μmol/L	17 μmol/L
		H = 84 μmol/L		H = 22 μmol/L
	ACC	N = NC	11 μmol/L	N = NC	NC
		H = 11 μmol/L		H = 60 μmol/L
	DGAT	N = NC	46 μmol/L	N = NC	NC
		H = NC		H = NC
	PDHK	N = 54 μmol/L	NC	N = 17 μmol/L	5.4 μmol/L
		H = NC		H = 46 μmol/L
Kinase targets	Pan PI3K	N = 0.1 μmol/L	0.02 μmol/L	N = 0.2 μmol/L	0.14 μmol/L
		H = 0.2 μmol/L		H = 0.3 μmol/L
	AKT	N = 20 μmol/L	0.36 μmol/L	N = 8.3 μmol/L	0.17 μmol/L
		H = 29 μmol/L		H = 8.6 μmol/L
	mTOR	N = 0.8 μmol/L	0.1 μmol/L	N = 1 μmol/L	0.12 μmol/L
		H = 0.7 μmol/L		H = 1.4 μmol/L

NOTE: In 2D growth, cells were incubated under normoxia (N) and hypoxia (H). Results are shown as concentration of the drug that inhibited 50% growth (growth inhibition 50%–GI₅₀), calculated using GraphPrism nonlinear regression (curve fit).

Abbreviation: NC, not calculated due to poor curve fit or no loss in cell viability with highest concentration.