Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models
Abstract 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) enha...
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| Veröffentlicht in: | Journal of radiation research 2022-01, Vol.63 (1), p.19-29 |
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| creator | Inamasu, Eiko Tsuchiya, Tomoshi Yamauchi, Motohiro Nishi, Kodai Matsuda, Katsuya Sugawara, Fumio Sakaguchi, Kengo Mori, Ryoichi Matsumoto, Keitaro Miyazaki, Takuro Hatachi, Go Doi, Ryoichiro Watanabe, Hironosuke Tomoshige, Koichi Matsuda, Naoki Higami, Yoshikazu Shimokawa, Isao Nakashima, Masahiro Nagayasu, Takeshi |
| description | Abstract
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. |
| doi_str_mv | 10.1093/jrr/rrab090 |
| format | Article |
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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.</description><identifier>ISSN: 0449-3060</identifier><identifier>EISSN: 1349-9157</identifier><identifier>DOI: 10.1093/jrr/rrab090</identifier><identifier>PMID: 34738103</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>Animals ; Antineoplastic Agents - therapeutic use ; Cell Line, Tumor ; Fundamental Radiation Science ; Humans ; Male ; Mesothelioma - drug therapy ; Mesothelioma - metabolism ; Mesothelioma - radiotherapy ; Mesothelioma, Malignant ; Mice ; Mice, Nude ; Pleural Neoplasms - drug therapy ; Pleural Neoplasms - metabolism ; Pleural Neoplasms - radiotherapy ; Radiation Tolerance</subject><ispartof>Journal of radiation research, 2022-01, Vol.63 (1), p.19-29</ispartof><rights>The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology. 2021</rights><rights>The Author(s) 2021. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c467t-cd16d182e908770aecd4a4612902fd199668ea244c0dc6b83b9109463d3076083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776698/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8776698/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1603,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34738103$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Inamasu, Eiko</creatorcontrib><creatorcontrib>Tsuchiya, Tomoshi</creatorcontrib><creatorcontrib>Yamauchi, Motohiro</creatorcontrib><creatorcontrib>Nishi, Kodai</creatorcontrib><creatorcontrib>Matsuda, Katsuya</creatorcontrib><creatorcontrib>Sugawara, Fumio</creatorcontrib><creatorcontrib>Sakaguchi, Kengo</creatorcontrib><creatorcontrib>Mori, Ryoichi</creatorcontrib><creatorcontrib>Matsumoto, Keitaro</creatorcontrib><creatorcontrib>Miyazaki, Takuro</creatorcontrib><creatorcontrib>Hatachi, Go</creatorcontrib><creatorcontrib>Doi, Ryoichiro</creatorcontrib><creatorcontrib>Watanabe, Hironosuke</creatorcontrib><creatorcontrib>Tomoshige, Koichi</creatorcontrib><creatorcontrib>Matsuda, Naoki</creatorcontrib><creatorcontrib>Higami, Yoshikazu</creatorcontrib><creatorcontrib>Shimokawa, Isao</creatorcontrib><creatorcontrib>Nakashima, Masahiro</creatorcontrib><creatorcontrib>Nagayasu, Takeshi</creatorcontrib><title>Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models</title><title>Journal of radiation research</title><addtitle>J Radiat Res</addtitle><description>Abstract
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.</description><subject>Animals</subject><subject>Antineoplastic Agents - therapeutic use</subject><subject>Cell Line, Tumor</subject><subject>Fundamental Radiation Science</subject><subject>Humans</subject><subject>Male</subject><subject>Mesothelioma - drug therapy</subject><subject>Mesothelioma - metabolism</subject><subject>Mesothelioma - radiotherapy</subject><subject>Mesothelioma, Malignant</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Pleural Neoplasms - drug therapy</subject><subject>Pleural Neoplasms - metabolism</subject><subject>Pleural Neoplasms - radiotherapy</subject><subject>Radiation Tolerance</subject><issn>0449-3060</issn><issn>1349-9157</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kc2OFCEUhYnROO3oyr1hZUxMOZeCpoqNyWTiXzKJG10TGm51M6GghKpO-gV8n3kRn0k63U504wbI5eNc7jmEvGTwjoHiV3c5X-VsNqDgEVkxLlSj2Lp7TFYg6pmDhAvyrJQ7gLaDNTwlF1x0vGfAV-TndZy9NdFipmaLcaa_7puyhCH9WHxM-1QOoTH2EKacJhPR-RQoxt3xRaHzDmk2tVYwFj_7vZ8PNA10t4wm0tEEv42mao5YUmWDT6OhPtK4OKRjWspxdRjKc_JkMKHgi_N-Sb5__PDt5nNz-_XTl5vr28YK2c2NdUw61reooO86MGidMEKyVkE7OKaUlD2aVggLzspNzzeqWiQkdxw6CT2_JO9PutOyGdHZOnA2QU_ZjyYfdDJe_3sT_U5v017XdlKqo8Cbs0CuDmGZ9eiLxRCqN3Ue3a6VaNVaKlbRtyfU5lRKxuGhDQN9TE7X5PQ5uUq_-vtnD-yfqCrw-gSkZfqv0m_JiahO</recordid><startdate>20220120</startdate><enddate>20220120</enddate><creator>Inamasu, Eiko</creator><creator>Tsuchiya, Tomoshi</creator><creator>Yamauchi, Motohiro</creator><creator>Nishi, Kodai</creator><creator>Matsuda, Katsuya</creator><creator>Sugawara, Fumio</creator><creator>Sakaguchi, Kengo</creator><creator>Mori, Ryoichi</creator><creator>Matsumoto, Keitaro</creator><creator>Miyazaki, Takuro</creator><creator>Hatachi, Go</creator><creator>Doi, Ryoichiro</creator><creator>Watanabe, Hironosuke</creator><creator>Tomoshige, Koichi</creator><creator>Matsuda, Naoki</creator><creator>Higami, Yoshikazu</creator><creator>Shimokawa, Isao</creator><creator>Nakashima, Masahiro</creator><creator>Nagayasu, Takeshi</creator><general>Oxford University Press</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20220120</creationdate><title>Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models</title><author>Inamasu, Eiko ; Tsuchiya, Tomoshi ; Yamauchi, Motohiro ; Nishi, Kodai ; Matsuda, Katsuya ; Sugawara, Fumio ; Sakaguchi, Kengo ; Mori, Ryoichi ; Matsumoto, Keitaro ; Miyazaki, Takuro ; Hatachi, Go ; Doi, Ryoichiro ; Watanabe, Hironosuke ; Tomoshige, Koichi ; Matsuda, Naoki ; Higami, Yoshikazu ; Shimokawa, Isao ; Nakashima, Masahiro ; Nagayasu, Takeshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c467t-cd16d182e908770aecd4a4612902fd199668ea244c0dc6b83b9109463d3076083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - therapeutic use</topic><topic>Cell Line, Tumor</topic><topic>Fundamental Radiation Science</topic><topic>Humans</topic><topic>Male</topic><topic>Mesothelioma - drug therapy</topic><topic>Mesothelioma - metabolism</topic><topic>Mesothelioma - radiotherapy</topic><topic>Mesothelioma, Malignant</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Pleural Neoplasms - drug therapy</topic><topic>Pleural Neoplasms - metabolism</topic><topic>Pleural Neoplasms - radiotherapy</topic><topic>Radiation Tolerance</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Inamasu, Eiko</creatorcontrib><creatorcontrib>Tsuchiya, Tomoshi</creatorcontrib><creatorcontrib>Yamauchi, Motohiro</creatorcontrib><creatorcontrib>Nishi, Kodai</creatorcontrib><creatorcontrib>Matsuda, Katsuya</creatorcontrib><creatorcontrib>Sugawara, Fumio</creatorcontrib><creatorcontrib>Sakaguchi, Kengo</creatorcontrib><creatorcontrib>Mori, Ryoichi</creatorcontrib><creatorcontrib>Matsumoto, Keitaro</creatorcontrib><creatorcontrib>Miyazaki, Takuro</creatorcontrib><creatorcontrib>Hatachi, Go</creatorcontrib><creatorcontrib>Doi, Ryoichiro</creatorcontrib><creatorcontrib>Watanabe, Hironosuke</creatorcontrib><creatorcontrib>Tomoshige, Koichi</creatorcontrib><creatorcontrib>Matsuda, Naoki</creatorcontrib><creatorcontrib>Higami, Yoshikazu</creatorcontrib><creatorcontrib>Shimokawa, Isao</creatorcontrib><creatorcontrib>Nakashima, Masahiro</creatorcontrib><creatorcontrib>Nagayasu, Takeshi</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of radiation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Inamasu, Eiko</au><au>Tsuchiya, Tomoshi</au><au>Yamauchi, Motohiro</au><au>Nishi, Kodai</au><au>Matsuda, Katsuya</au><au>Sugawara, Fumio</au><au>Sakaguchi, Kengo</au><au>Mori, Ryoichi</au><au>Matsumoto, Keitaro</au><au>Miyazaki, Takuro</au><au>Hatachi, Go</au><au>Doi, Ryoichiro</au><au>Watanabe, Hironosuke</au><au>Tomoshige, Koichi</au><au>Matsuda, Naoki</au><au>Higami, Yoshikazu</au><au>Shimokawa, Isao</au><au>Nakashima, Masahiro</au><au>Nagayasu, Takeshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models</atitle><jtitle>Journal of radiation research</jtitle><addtitle>J Radiat Res</addtitle><date>2022-01-20</date><risdate>2022</risdate><volume>63</volume><issue>1</issue><spage>19</spage><epage>29</epage><pages>19-29</pages><issn>0449-3060</issn><eissn>1349-9157</eissn><abstract>Abstract
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.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>34738103</pmid><doi>10.1093/jrr/rrab090</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antineoplastic Agents - therapeutic use Cell Line, Tumor Fundamental Radiation Science Humans Male Mesothelioma - drug therapy Mesothelioma - metabolism Mesothelioma - radiotherapy Mesothelioma, Malignant Mice Mice, Nude Pleural Neoplasms - drug therapy Pleural Neoplasms - metabolism Pleural Neoplasms - radiotherapy Radiation Tolerance |
| title | Anticancer agent α-sulfoquinovosyl-acylpropanediol enhances the radiosensitivity of human malignant mesothelioma in nude mouse models |
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