| Shao Lening,Zhu Baosong,Yang Xiaodong,et al.Rapamycin affects radiosensitivity of colorectal cancer by activating the autophagy of M2 macrophage[J].Chinese Journal of Radiological Medicine and Protection,2022,42(9):657-663 |
| Rapamycin affects radiosensitivity of colorectal cancer by activating the autophagy of M2 macrophage |
| Received:June 06, 2022 |
| DOI：10.3760/cma.j.cn112271-20220606-00240 |
| KeyWords:Rapamycin M2 macrophages Autophagy Colorectal cancer Radiation sensitivity |
| FundProject:省部共建放射医学与辐射防护国家重点实验室开放课题(GZK1202010,GZK1202021) |
| Author Name | Affiliation | E-mail | | Shao Lening | Department of Gastrointestinal Surgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | | | Zhu Baosong | Suzhou Hospital of Traditional Chinese Medicine, Suzhou 215007, China | | | Yang Xiaodong | Department of Gastrointestinal Surgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | | | Cao Jianping | School of Radiation Medicine and Protection, State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou 215123, China | | | Xing Chungen | Department of Gastrointestinal Surgery, Second Affiliated Hospital of Soochow University, Suzhou 215004, China | xingcg@126.com |
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| Abstract:: |
| Objective To investigate the effects of rapamycin on the autophagy activation of M2 macrophages and the radiosensitivity in colorectal cancer xenograft.Methods THP-1 cells were induced into Type-Ⅱ macrophages with PMA and/or IL-4.Rapamycin and Bafilomycin A1 were uesd to activate and suppress autophagy of M2 macrophage,respectively.Colorectal cancer LoVo cells were inoculated on BALB/c-nu/nu nude mice.After the xenograft tumor size approached to 10 mm in diameter,the nude mice were divided into the following groups randomly:M2 macrophage autophagy inactive group and active group,autophagy downregulation of the activated group,and nontreatment control group.The tumors in mice were irradiated with 8 Gy X-rays in two fractions,and the radiosensitivity of colorectal cancer xenograft in each group was analyzed.Results The expression levels of M2 macrophage markers Arg-1 and CCL-22 were significantly higher than those in M0 macrophage.The tumor weight,volume[(1.93±0.05) g,(2.14±0.06) cm3]and micro-vessel density (36.37±1.04) in M2 autophagy inactive group were higher than those in control group[(1.35±0.05) g,(1.77±0.02) cm3,25.69±1.34](t=20.07,14.56,10.92,P < 0.05).After activation of M2 autophagy,the tumor weight,volume and micro-vessel density were significantly decreased to (0.89±0.03) g,(1.24±0.01) cm3,and 13.60±1.52(t=44.37,40.32,21.43,P< 0.05).After down-regulation of M2 autophagy with bafilomycin A1,the tumor weight,volume and micro-vessel density were increased to (1.02±0.07) g,(1.37±0.02) cm3,and 21.06±1.41(t=4.67,13.79,6.23,P < 0.05).Autophagy inaction suppressed the expression of Livin and Survivin in tumor (t=2.64,7.90,P < 0.05),and the activation of M2 autophagy further down-regulated the expression of Livin,Survivin (t=5.43,9.39,P < 0.05).The expression levels of Livin and Survivin were increased after the treatment with bafilomycin A1(t=2.80,3.17,P<0.05).Conclusions M2 macrophagy promoted the growth of colorectal cancer xenograft by inducing the formation of micro-vessels in the tumor,which is one of the mechanisms of tumor-associated macrophages participating in the radiotherapy resistance of colorectal cancer.Activation of M2 autophagy by rapamycin inhibited the ability of M2 macrophagy in promoting tumor growth,and induced apoptosis of colorectal cancer cells after radiotherapy by down-regulating the expression of anti-apoptotic genes Livin and Survivin,thus increased the radiosensitivity of colorectal cancer. |
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