Fig. 6

Lovastatin and ERRα inverse agonist enhance the sensitivity of EGFR-TKIs. a Cells were treated with gefitinib or osimertinib, gefitinib or osimertinib+ 10 μM lovastatin, gefitinib or osimertinib+ 10 μM lovastatin+ 100 μM mevalonate, gefitinib or osimertinib+ 10 μM lovastatin+ 10 μM cholesterol for 48 h. Then cell viability was measured by MTT assay. b Cells were treated with gefitinib or osimertinib, along with lovastatin, lovastatin+ cholesterol, lovastatin+ XCT790, lovastatin+ cholesterol+ XCT790. Then cell viability was measured by MTT assay. c Cell cycle distribution was analyzed by flow cytometry after treatment with lovastatin, lovastatin+ MVA, lovastatin+ XCT790, lovastatin+ MVA+ XCT790. d-j Primary tumor gross appearance, e growth curves, f body weight, and g tumor weight of the PC-9/GR xenograft after treatment with indicated drugs for 21 days. h Cholesterol level in tumor tissue was determined. i Western blot assay measured ERRα protein level. j IHC staining detected Ki67 and ERRα expression in the indicated tumors. Data are expressed as mean ± SEM (n = 3) *p < 0.05, **p < 0.01, ***p < 0.001 compared to control; ^$p < 0.05, ^$$p < 0.01, ^$$$p < 0.001 compared to lovastatin in b and c. Data are expressed as mean ± SEM (n = 3) **p < 0.01, ***p < 0.001in h and i. Data are expressed as mean ± SEM (n = 5) *p < 0.05, **p < 0.01 in g