High-intensity focused ultrasound enhances the cisplatin sensitivity to human non-small cell lung cancer in vitro and in vivo

Abstract BackgroundThe incidence and mortality of non-small cell lung cancer (NSCLC) rank first among malignant tumors worldwide. Cisplatin (CDDP) is currently the first-line chemotherapy drug used in clinical practice. However, the underlying mechanism that NSCLC cells are resistant to CDDP has not been fully elucidated. Therefore, it is urgent to explore the exact function of chemotherapy resistance and improve the anti-tumor effect of CDDP treatment.MethodWe investigated the surviving fraction of H1299 and A549 cells treated with different High-intensity focused ultrasound (HIFU) and various CDDP concentrations. HIFU (400W/cm2) and CDDP (10 μM) were selected to probe the further function in H1299 and A549 cells. Flow cytometry, MTT, and colony formation assays were performed to evaluate the apoptosis and proliferative effect of HIFU and CDDP on NSCLC cells. Transwell assays were used to analyze the migration and invasion abilities of NSCLC cells with HIFU and CDDP treatments. Platinum (Pt) accumulation was further measured in H1299 and A549 cells with different treatments. Finally, An NSCLC patient-derived xenograft model was used to explore the effect of HIFU and CDDP on NSCLC tumor growth.ResultsHIFU combined with CDDP can markedly reduce the surviving rate and promote the apoptosis of NSCLC cells. Furthermore, co-treatment with HIFU and CDDP significantly inhibited the proliferation, colony formation, migration, and invasion of NSCLC cells compared to that with any single treatment. Moreover, the combined therapy can effectively promote Pt accumulation in NSCLC cells. Further functional analysis suggested that HIFU combined with CDDP can inhibit tumor growth in an NSCLC patient-derived xenograft model. Finally, the CDDP method effectively upregulated the expression level of apoptosis-related protein, cleaved-PARP, which could be further enhanced by the HIFU treatment.ConclusionOur results revealed that HIFU enhances the anti-NSCLC effect of CDDP both in vitro and in vivo, providing a promising combination therapy for clinical NSCLC treatment.