Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models

Eiko Inamasu, Tomoshi Tsuchiya, Motohiro Yamauchi, Kodai Nishi, Katsuya Matsuda, Fumio Sugawara, Kengo Sakaguchi, Ryoichi Mori, Keitaro Matsumoto, Takuro Miyazaki, Go Hatachi, Ryoichiro Doi, Hironosuke Watanabe, Koichi Tomoshige, Naoki Matsuda, Yoshikazu Higami, Isao Shimokawa, Masahiro Nakashima, Takeshi Nagayasu

研究成果: ジャーナルへの寄稿学術誌査読

抄録

Malignant pleural mesothelioma (MPM) is a highly malignant disease that develops after asbestos exposure. Although the number of MPM cases is predicted to increase, no effective standard therapies have been established. The novel radiosensitizer α-sulfoquinovosyl-acylpropanediol (SQAP) enhances the effects of γ-radiation in human lung and prostate cancer cell lines and in animal models. In this study, we explored the radiosensitizing effect of SQAP and its mechanisms in MPM. The human MPM cell lines MSTO-211H and MESO-4 were implanted subcutaneously into the backs and thoracic cavities of immunodeficient KSN/Slc mice, then 2 mg/kg SQAP was intravenously administered with or without irradiation with a total body dose of 8 Gy. In both the orthotopic and ectopic xenograft murine models, the combination of irradiation plus SQAP delayed the implanted human MSTO-211H tumor growth. The analysis of the changes in the relative tumor volume of the MSTO-211H indicated a statistically significant difference after 8 Gy total body combined with 2 mg/kg SQAP, compared to both the untreated control (P = 0.0127) and the radiation treatment alone (P = 0.0171). After the treatment in each case, immunostaining of the harvested tumors revealed decreased cell proliferation, increased apoptosis and normalization of tumor blood vessels in the SQAP- and irradiation-treated group. Furthermore, hypoxia-inducible factor (HIF) 1 mRNA and protein expression were decreased, indicating reoxygenation in this group. In conclusion, SQAP improved hypoxic conditions in tumor tissue and may elicit a radiosensitizing effect in malignant mesothelioma models.

本文言語英語
ページ(範囲)19-29
ページ数11
ジャーナルJournal of radiation research
63
1
DOI
出版ステータス出版済み - 1月 20 2022

!!!All Science Journal Classification (ASJC) codes

  • 放射線
  • 放射線学、核医学およびイメージング
  • 健康、毒物学および変異誘発

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