Synergistic effects of combined treatment with ultrasound‐mediated cisplatin‐loaded microbubbles and atorvastatin on head and neck cancer

Abstract

Background: Previously, we used ultrasound (US)-mediated cisplatin (CDDP)-loaded microbubbles (CDDP-MBs) to increase intratumoral CDDP level while decreasing systemic cytotoxicity. Statins have shown antitumorigenic properties. Our study investigated the effects of atorvastatin with CDDP-MBs and US on head neck cancer. Methods: Cell viability analysis with CDDP-MBs and atorvastatin combined with US in FaDu cell line were tested. Cell proliferation and glutathione level were also evaluated. Results: Both CDDP and atorvastatin reduced cell's viability. Coadministration of CDDP and atorvastatin resulted in synergistic inhibitory effect. After US sonication, cell viability with atorvastatin and CDDP was significantly reduced for CDDP combined with MBs (65.98% to 49.13%) and for CDDP-MBs (86.17% to 50.15%). CDDP-MBs combined with atorvastatin and US inhibited the proliferation of cells: 19.61% for CDDP-MBs + atorvastatin + US, 36.28% for CDDP + atorvastatin, and 71.73% for atorvastatin alone. Also, CDDP-MBs + atorvastatin + US induced apoptosis by decreasing cellular level of glutathione. Conclusions: Atorvastatin combined with MB-conjugated CDDP exerts synergistic inhibitory effect on head neck cancer.

Cisplatin for cancer therapy and overcoming chemoresistance

“…Ultrasound -guided delivery of cisplatin-loaded microbubbles was effective in HNSCC with reduced systemic cytotoxicity and the same microbubbles loaded with both cisplatin and statins (atorvastatin) acted synergistically inhibitory towards HNSCC progression. These inhibitory anticancer effects were achieved by inducing cancer cell apoptosis that reduced tumour viability with a concurrent decrease in cellular glutathione [ 183 ]. An evaluation of cisplatin efficacy in the head and neck carcinoma-mimicking cell lines (FaDu and PE/CA-PJ49) combined with resveratrol (shown to reduce cisplatin toxicity and increase cell viability in normal HaCaT cells) revealed the induction of apoptosis in FaDu cells.…”