LAUSR

Abstract Purpose: The aim of tumor-specific chemoradiotherapy is to achieve synergistic anticancer effects with clinically acceptable toxicity. Our previous studies showed that Pluronic P85 augments radiation cancer cell killing of (±)-gossypol in vitro. In this study, the radiosensitizing effect of (−)-gossypol, more potent Bcl protein inhibitor, with Pluronic P85 was investigated. Materials and methods: The inhibitory effect of (−)-gossypol solubilized Pluronic P85 with 0–8 Gy of radiation on clonogenic survival rate of A549 human lung adenocarcinoma cells was investigated in vitro. The anticancer effect of (−)-gossypol-solubilized Pluronic P85 with fractionated radiation of 15 Gy was assessed by A549 tumor-bearing mice. Results: (-)-Gossypol-loaded Pluronic P85 was found to be a more potent radiosensitizer in vitro. Pluronic P85 increased the anti-proliferative activity of (−)-gossypol against A549 cells (82 ± 42 versus 190 ± 60 nM). In addition, the combination of P85 and (−)-gossypol effectively reduced clonogenic survival of A549 cells: (11 ± 5%) compared to (−)-gossypol and P85 alone (62 ± 27% and 93 ± 13%, respectively), and enhanced radiation cancer cell killing. In vivo, P85 (200 mg/kg/day) and (−)-gossypol (15 mg/kg/day) could be safely injected intravenously over 5 days and enhanced radiation-related tumor control in an A549 xenograft model. Conclusion: Pluronic P85 and (−)-gossypol act as a novel dual agent radiosensitizer and holds promise as a chemoradiotherapeutic strategy.