Fig. 6: Effect of CPT, Capmatinib and THEMIS2 on the chemosensitivity, pulmonary metastasis and tumor growth in TNBC cells.

A Dose-dependent growth inhibition of MDA-MB-231 and Hs578T cells under continuous exposure to the indicated concentrations of docetaxel or carboplatin for 24 h was measured using an MTT assay. Cells were divided into two groups according to treatment with CPT (20 μM) or dimethyl sulfoxide. B Dose-dependent growth inhibition of MDA-MB-231 and Hs578T cells transfected with control or THEMIS2 siRNA for 8 h, serum starved for 24 h, and upon continuous exposure to the indicated concentrations of docetaxel or carboplatin for 24 h was measured using an MTT assay. C The lung weights of four groups of CB17-SCID mice that had received tail vein injections of MDA-MB-231-IV2 cells that had been transfected with the indicated siRNAs or plasmids with or without treatment with CPT (15 mg/kg) were compared using a two-tailed Mann–Whitney test. The scatter plot represents means ± SEs from five mice in each group (*P < 0.05; **P < 0.01). Representative pictures of the pulmonary metastatic tumors and lung metastasis index of the mentioned four mice groups are shown; specimens were stained with hematoxylin and eosin. D Lung metastasis of mice, which were tail vein injected with 1 × 10⁶ MDA-MB-231 cells followed by treatment with or without CPT (15 mg/kg). E Docetaxel treatment substantially reduced tumor size, whereas THEMIS2 overexpression increased chemoresistance in vivo (n = 5 for each group). Left: tumor growth was monitored; right: CB17-SCID mice were categorized into four groups according to the treatment with docetaxel (100 μg/week) as indicated. In each group, 5 × 10⁵ Hs578T-FPI cells were injected into the mammary fat pads of CB17-SCID mice. F Capmatinib treatment substantially reduced tumor size, whereas THEMIS2 overexpression further increased the drug sensitively. Tumor growth was monitored. CB17-SCID mice were categorized into four groups according to the treatment with Capmatinib (8 mg/kg daily) with or without THEMIS2 over expression as indicated. In each group, 1 × 10⁶ MDA-MB-231 cells stably transfected with the indicated plasmids were injected into the mammary fat pads of CB17-SCID mice (n = 6 for each group). The quantification of tumor weight of the excised tumors of all treatment groups was performed. G Left, CB17-SCID mice were orthotopically injected with 1×10⁶ MDA-MB-231 cells followed by treatment with docetaxel alone or in combination with Capmatinib. Tumor growth was monitored in four groups as indicated (n = 10 for each group). Right, survival analysis of the four indicated groups. All mice were sacrificed 30-60 days after implantation. All in vitro experiments (A and B) were performed in triplicate and repeated three times (*P < 0.05). The data in C, D, E, F, G represent means ± SEs from two to three independent experiments (*P < 0.05; **P < 0.01).