Fig. 5: SLC7A5-Regulated Olaparib Resistance and Tumorigenesis via ERBB2.

A–C Cell Function Experiments. ERBB2 knockdown reverses olaparib resistance induced by SLC7A5 overexpression. A Clonogenic Assay. B Apoptosis Assay. C Cell Viability Assay. D, E Kaplan−Meier survival curves of nude mice implanted orthotopically with CAOV-3 cells. In a xenograft survival study conducted in nude mice, 5 million CAOV-3 cells were subcutaneously injected. D Mice were divided into three groups, NC + shCtrl, SLC7A5 + shCtrl, and shSLC7A5 + shERBB2, with 20 mice per group. Once the tumors reached a volume of 50 mm³, each group was randomly divided into control and treatment subgroups. The treatment subgroup received olaparib every other day for a total of eight doses at 25 mg/kg, while the control group received an equivalent volume of DMSO. In accordance with animal ethics, mice were euthanized when tumor volumes reached 1000 mm³, which was recorded as the endpoint for survival. The median survival times were as follows. 27.5 days for the (NC + shCtrl + DMSO) group, 15 days for the (SLC7A5 + shCtrl + DMSO) group, 30 days for the (SLC7A5 + shERBB2 + DMSO) group, 45 days for the (NC + shCtrl + Olaparib) group, 20 days for the (SLC7A5 + shCtrl + Olaparib) group, and 47.5 days for the (NC + shCtrl +Olaparib) group (n = 10). E The relative extension of survival was statistically analyzed following olaparib treatment. All the in vitro data were obtained from at least three independent experiments. Error bars represent standard deviation. * = P < 0.05, ** = P < 0.001, *** = P < 0.0001, ns = non-significant compared to normal or control treatment. F Clonogenic Assay. The knockdown of ERBB2 inhibits the proliferative effects induced by the overexpression of SLC7A5. G–K In vivo experiments. Subcutaneous implantation of CAOV-3 cells showed that ERBB2 inhibits SLC7A5-mediated tumor promotion. G Tumor. H Tumor Volume(mm³). I Tumor Weight (g). J Immunohistochemistry (IHC). K Western Blot Analysis. All in vitro data points are derived from at least three independent experiments. Error bars represent the standard deviation. Statistical significance is indicated by the following symbols. * = P < 0.05, ** = P < 0.001, *** = P < 0.0001, ns = non-significant compared to normal or control treatment.