Multimodality imaging assessments of response to metformin therapy for breast cancer in nude mice
Background Metformin is the most widely used anti-diabetic drug in the world.An increasing body of evidence shows metformin also blocks cell cycle progression and selectively induces apoptosis via caspase activation in some breast tumor cells.Diffusion-weighted imaging (DWl) and bioluminescence imag...
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description | Background Metformin is the most widely used anti-diabetic drug in the world.An increasing body of evidence shows metformin also blocks cell cycle progression and selectively induces apoptosis via caspase activation in some breast tumor cells.Diffusion-weighted imaging (DWl) and bioluminescence imaging (BLI) have great potential in the evaluation of the early response to cancer therapies.We used DWl and BLI in evaluating the response of breast cancer to metformin.Methods The luciferase-engineered human breast cancer cell line MDA-MB-231 was inoculated into the mammary fat pad of nude mice.Twelve female nude mice bearing tumors were divided into two groups.The mice in the treatment group received metformin (2 mg/ml in drinking water daily) after tumor inoculation,and the mice in the control group were offered drinking water without any drug added.We performed 7T magnetic resonance imaging and optical imaging every week.Imaging included T1-and T2-weighted imaging,DWl,and BLI.After imaging.The tumors were collected and subjected to histological analysis.Results The mean photons/second of tumors in the treatment group was (3.00±0.43)×106 at day one,(1.01±0.14)×107 at 2 weeks,(5.79±1.42)×107 at 4 weeks,and (2.33±0.70)×107 at 8 weeks.The mean photons/second of tumors in the control group was (3.29±0.59)×106 at day one,(3.59±0.63)×107 at 2 weeks,(3.87±0.56)×108 at 4 weeks,and (4.12±1.72)x108 at 8 weeks.Compared to the control group,the treatment group showed an obvious decrease in the mean bioluminescence (photons/s) of the tumors and fewer metastases.Histological examination confirmed the presence of fewer metastases.DWI showed the apparent diffusion coefficient (ADC) value of the tumors; the mean ADC value was (0.9287±0.04346)x10-3 mm2/s in the treated tumors and (0.7553±0.01804)x103 mm2/s in the untreated tumors.The ADC value of tumors in the treatment group was significantly higher than the control tumors (P=0.0013).Conclusions The growth and metastasis of MDA-MB-231 breast cancer may be inhibited by metformin.DWI and BLI have great potentials in the evaluation of the early response to metformin treatment.BLI has a high degree of sensitivity and is able to detect micrometastasis,thus can be used for identifying tumor metastasis in vivo. |
doi_str_mv | 10.3760/cma.j.issn.0366-6999.20122806 |
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Ltd. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c437t-fc98e50c28ccba64f87322a72f6dcadf219aadfb0c299a6b14b72026074961673</citedby><cites>FETCH-LOGICAL-c437t-fc98e50c28ccba64f87322a72f6dcadf219aadfb0c299a6b14b72026074961673</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/85656X/85656X.jpg</thumbnail><link.rule.ids>314,780,784,864,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24112170$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mao, Yi</creatorcontrib><creatorcontrib>Xia, Rui</creatorcontrib><creatorcontrib>Wang, Lei</creatorcontrib><creatorcontrib>Wang, Yu-qing</creatorcontrib><creatorcontrib>Gao, Fa-bao</creatorcontrib><title>Multimodality imaging assessments of response to metformin therapy for breast cancer in nude mice</title><title>Chinese medical journal</title><addtitle>Chinese Medical Journal</addtitle><description>Background Metformin is the most widely used anti-diabetic drug in the world.An increasing body of evidence shows metformin also blocks cell cycle progression and selectively induces apoptosis via caspase activation in some breast tumor cells.Diffusion-weighted imaging (DWl) and bioluminescence imaging (BLI) have great potential in the evaluation of the early response to cancer therapies.We used DWl and BLI in evaluating the response of breast cancer to metformin.Methods The luciferase-engineered human breast cancer cell line MDA-MB-231 was inoculated into the mammary fat pad of nude mice.Twelve female nude mice bearing tumors were divided into two groups.The mice in the treatment group received metformin (2 mg/ml in drinking water daily) after tumor inoculation,and the mice in the control group were offered drinking water without any drug added.We performed 7T magnetic resonance imaging and optical imaging every week.Imaging included T1-and T2-weighted imaging,DWl,and BLI.After imaging.The tumors were collected and subjected to histological analysis.Results The mean photons/second of tumors in the treatment group was (3.00±0.43)×106 at day one,(1.01±0.14)×107 at 2 weeks,(5.79±1.42)×107 at 4 weeks,and (2.33±0.70)×107 at 8 weeks.The mean photons/second of tumors in the control group was (3.29±0.59)×106 at day one,(3.59±0.63)×107 at 2 weeks,(3.87±0.56)×108 at 4 weeks,and (4.12±1.72)x108 at 8 weeks.Compared to the control group,the treatment group showed an obvious decrease in the mean bioluminescence (photons/s) of the tumors and fewer metastases.Histological examination confirmed the presence of fewer metastases.DWI showed the apparent diffusion coefficient (ADC) value of the tumors; the mean ADC value was (0.9287±0.04346)x10-3 mm2/s in the treated tumors and (0.7553±0.01804)x103 mm2/s in the untreated tumors.The ADC value of tumors in the treatment group was significantly higher than the control tumors (P=0.0013).Conclusions The growth and metastasis of MDA-MB-231 breast cancer may be inhibited by metformin.DWI and BLI have great potentials in the evaluation of the early response to metformin treatment.BLI has a high degree of sensitivity and is able to detect micrometastasis,thus can be used for identifying tumor metastasis in vivo.</description><subject>Animals</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Diffusion Magnetic Resonance Imaging</subject><subject>Female</subject><subject>Luminescent Measurements</subject><subject>Metformin - therapeutic use</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Multimodal Imaging</subject><subject>Neoplasm Metastasis</subject><subject>乳腺癌</subject><subject>二甲双胍</subject><subject>光成像</subject><subject>多模式</subject><subject>平均光子数</subject><subject>癌症治疗</subject><subject>裸鼠</subject><subject>评估</subject><issn>0366-6999</issn><issn>2542-5641</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kc1u3CAUhVHVqpmmfYWKLhp1Y5c_g1l0EUX9k1Jl064RxjBjy8AEsKrJ04fRTGZ1dcV3OdJ3APiMUUsFR1-N1-3cTjmHFlHOGy6lbAnChPSIvwIb0jHSdJzh12BzAa7Au5xnhEjXCf4WXBGGMcECbYD-sy5l8nHUy1QOcPJ6O4Ut1DnbnL0NJcPoYLJ5H0O2sETobXEx-SnAsrNJ7w-wrnBIVucCjQ7GJlgfwzpa6Cdj34M3Ti_ZfjjPa_Dvx_e_d7-a-4efv-9u7xvDqCiNM7K3HTKkN2bQnLleUEK0II6PRo-OYKnrGCohpeYDZoMgiHAkmOSYC3oNbk7__tfB6bBVc1xTqInqaWf8XBVRLBEhFfxyAvcpPq42F-WnbOyy6GDjmhVmjFLJCO0q-u2EmhRzTtapfaqK0kFhpI51qFqHmtWxDnW0rY621Usd9f7jOWodvB0v1y_-K_DpHLCLYftY1V8YJlgneibpM0ljlcQ</recordid><startdate>2013</startdate><enddate>2013</enddate><creator>Mao, Yi</creator><creator>Xia, Rui</creator><creator>Wang, Lei</creator><creator>Wang, Yu-qing</creator><creator>Gao, Fa-bao</creator><general>Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W91</scope><scope>~WA</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>2B.</scope><scope>4A8</scope><scope>92I</scope><scope>93N</scope><scope>PSX</scope><scope>TCJ</scope></search><sort><creationdate>2013</creationdate><title>Multimodality imaging assessments of response to metformin therapy for breast cancer in nude mice</title><author>Mao, Yi ; Xia, Rui ; Wang, Lei ; Wang, Yu-qing ; Gao, Fa-bao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c437t-fc98e50c28ccba64f87322a72f6dcadf219aadfb0c299a6b14b72026074961673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Breast Neoplasms - drug therapy</topic><topic>Breast Neoplasms - pathology</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Diffusion Magnetic Resonance Imaging</topic><topic>Female</topic><topic>Luminescent Measurements</topic><topic>Metformin - therapeutic use</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Multimodal Imaging</topic><topic>Neoplasm Metastasis</topic><topic>乳腺癌</topic><topic>二甲双胍</topic><topic>光成像</topic><topic>多模式</topic><topic>平均光子数</topic><topic>癌症治疗</topic><topic>裸鼠</topic><topic>评估</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mao, Yi</creatorcontrib><creatorcontrib>Xia, Rui</creatorcontrib><creatorcontrib>Wang, Lei</creatorcontrib><creatorcontrib>Wang, Yu-qing</creatorcontrib><creatorcontrib>Gao, Fa-bao</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库-医药卫生</collection><collection>中文科技期刊数据库- 镜像站点</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>Wanfang Data Journals - Hong Kong</collection><collection>WANFANG Data Centre</collection><collection>Wanfang Data Journals</collection><collection>万方数据期刊 - 香港版</collection><collection>China Online Journals (COJ)</collection><collection>China Online Journals (COJ)</collection><jtitle>Chinese medical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mao, Yi</au><au>Xia, Rui</au><au>Wang, Lei</au><au>Wang, Yu-qing</au><au>Gao, Fa-bao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Multimodality imaging assessments of response to metformin therapy for breast cancer in nude mice</atitle><jtitle>Chinese medical journal</jtitle><addtitle>Chinese Medical Journal</addtitle><date>2013</date><risdate>2013</risdate><volume>126</volume><issue>19</issue><spage>3717</spage><epage>3722</epage><pages>3717-3722</pages><issn>0366-6999</issn><eissn>2542-5641</eissn><abstract>Background Metformin is the most widely used anti-diabetic drug in the world.An increasing body of evidence shows metformin also blocks cell cycle progression and selectively induces apoptosis via caspase activation in some breast tumor cells.Diffusion-weighted imaging (DWl) and bioluminescence imaging (BLI) have great potential in the evaluation of the early response to cancer therapies.We used DWl and BLI in evaluating the response of breast cancer to metformin.Methods The luciferase-engineered human breast cancer cell line MDA-MB-231 was inoculated into the mammary fat pad of nude mice.Twelve female nude mice bearing tumors were divided into two groups.The mice in the treatment group received metformin (2 mg/ml in drinking water daily) after tumor inoculation,and the mice in the control group were offered drinking water without any drug added.We performed 7T magnetic resonance imaging and optical imaging every week.Imaging included T1-and T2-weighted imaging,DWl,and BLI.After imaging.The tumors were collected and subjected to histological analysis.Results The mean photons/second of tumors in the treatment group was (3.00±0.43)×106 at day one,(1.01±0.14)×107 at 2 weeks,(5.79±1.42)×107 at 4 weeks,and (2.33±0.70)×107 at 8 weeks.The mean photons/second of tumors in the control group was (3.29±0.59)×106 at day one,(3.59±0.63)×107 at 2 weeks,(3.87±0.56)×108 at 4 weeks,and (4.12±1.72)x108 at 8 weeks.Compared to the control group,the treatment group showed an obvious decrease in the mean bioluminescence (photons/s) of the tumors and fewer metastases.Histological examination confirmed the presence of fewer metastases.DWI showed the apparent diffusion coefficient (ADC) value of the tumors; the mean ADC value was (0.9287±0.04346)x10-3 mm2/s in the treated tumors and (0.7553±0.01804)x103 mm2/s in the untreated tumors.The ADC value of tumors in the treatment group was significantly higher than the control tumors (P=0.0013).Conclusions The growth and metastasis of MDA-MB-231 breast cancer may be inhibited by metformin.DWI and BLI have great potentials in the evaluation of the early response to metformin treatment.BLI has a high degree of sensitivity and is able to detect micrometastasis,thus can be used for identifying tumor metastasis in vivo.</abstract><cop>China</cop><pub>Molecular Imaging Center, Department of Radiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China</pub><pmid>24112170</pmid><doi>10.3760/cma.j.issn.0366-6999.20122806</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Animals Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cell Line, Tumor Cell Proliferation - drug effects Diffusion Magnetic Resonance Imaging Female Luminescent Measurements Metformin - therapeutic use Mice Mice, Nude Multimodal Imaging Neoplasm Metastasis 乳腺癌 二甲双胍 光成像 多模式 平均光子数 癌症治疗 裸鼠 评估 |
title | Multimodality imaging assessments of response to metformin therapy for breast cancer in nude mice |
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