Fig. 6: Metabolic vulnerability of tumor cells resistant to molecular targeted drugs. | Nature Communications

Fig. 6: Metabolic vulnerability of tumor cells resistant to molecular targeted drugs.

From: mTOR-mediated cancer drug resistance suppresses autophagy and generates a druggable metabolic vulnerability

Fig. 6

T47D breast cancer cells were treated with increasing doses of alpelisib or pictilisib to obtain alpelisib-resistant (B7, H6) and pictilisib-resistant (B1, F3) subclones. a Cell viability of indicated T47D cells after 3 day treatment with alpelisib and pictilisib. Shown are mean ± SD, n = 3. b Western blot following treatment with alpelisib or pictilisib for 2 hours. c Autophagic flux assay. Parental and alpelisib/pictilisib-resistant LC3-HiBiT expressing T47D cells were pre-treated as indicated with chloroquine and AZD8055 for 48 hours and then with increasing doses 2DG/DCA for 6 hours. Shown is LC3-HiBiT reporter activity measured as luminescence normalized to untreated of n = 2 replicates. d Flow cytometry analysis for apoptosis (sub-G1). Shown are mean ± SD, n = 3, FDR q values. e Clonogenic growth of parental and alpelisib/pictilisib-resistant T47D cells treated with 2DG/DCA. Shown are representative images and quantification as mean ± SD, n = 3, two-way ANOVA with Dunnett’s multiple comparisons test.

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