氢质子磁共振频谱活体检测结肠癌耐药性的初步探讨
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摘要
目的探索1H-MRS活体检测结肠癌耐药性的可能性。方法 5只耐药(耐5-FU)与5只不耐药人类结肠癌SW480荷瘤裸鼠于肿瘤直径大于1.5cm时行1H-MRS检查,随后处死荷瘤鼠,切下肿瘤检测其PKC、P-gp、MRP1蛋白表达(Western Blot),观察肿瘤凋亡(TUNNEL法)。分析结肠癌耐药性与1H-MRS检测代谢物、肿瘤耐药基因表达、肿瘤凋亡的相关性。结果不耐药组人类结肠癌SW480裸鼠肿瘤的cho、lac、Lip及m I峰/cr面积比较耐药组人类结肠癌SW480/5-FU裸鼠增加,差别有统计学差异(P<0.05)。耐药组PKC、P-gp、MRP1蛋白表达明显高于不耐药组,差别有统计学差异(P<0.05)。在TUNNEL检测切片上,两组肿瘤组织均可见肿瘤细胞凋亡,两者差别无统计意义(P>0.05)。肿瘤代谢物cho、Lac、Lip、m I/cr与肿瘤耐药性呈正相关性;cho面积与肿瘤PKC表达光密度呈正相关,与肿瘤Pgp表达光密度呈正相关。结论肿瘤代谢物cho、lac、Lip的改变有可能有助于利用1H-MRS活体检测结肠癌耐药性改变。
Objective To exploration the feasibility to detect the drug resistance of human colon cancer in mice with magnetic resonance spectrum in vivo. Methods Nude mice with human colon cancer SW480(drug response) and 5 nude mice with SW480/5-Fu(5-Fu resistance) were given 1H-MRS examinations when the diameters of tumor were over 1.5 centimeters. Then these mouse models were sacrificed. Their tumors were removed and detected the protein expression of PKC, P-gp and MPR1(Western blot), apoptosis(TUNNEL). The correlation between metabolites detected with 1H-MRS and tumor drug resistance and the protein expression of PKC, P-gp and MPR1(Western blot), tumor apoptosis were analyized. Results The the area of cho, lac and Lip of tumors in SW480 group were significantly higher than that in SW480/5-Fu group(P<0.05). The protein expression of PKC, P-gp and MPR1 in SW480/5-Fu group were significantly higher than that of SW480 group(P<0.05). In the TUNNEL section, apoptotic cell were observed in two groups, and there is no significant difference between two groups(P>0.05). The area of cho, lac and Lip of tumors was positively correlated with drug resistance(r, P:0.870,0.001). The the area of cho has a positive correlation with the protein expression of PKC(r, P:0.745,0.013), P-gp(r, P:0.782,0.008). Conclusion Conclusion The change of metabolites cho, lac and Lip detected with 1H- MRS has the potential to help detection of colon cancer drug resistance with MR in vivo.
Objective To exploration the feasibility to detect the drug resistance of human colon cancer in mice with magnetic resonance spectrum in vivo. Methods Nude mice with human colon cancer SW480(drug response) and 5 nude mice with SW480/5-Fu(5-Fu resistance) were given 1H-MRS examinations when the diameters of tumor were over 1.5 centimeters. Then these mouse models were sacrificed. Their tumors were removed and detected the protein expression of PKC, P-gp and MPR1(Western blot), apoptosis(TUNNEL). The correlation between metabolites detected with 1H-MRS and tumor drug resistance and the protein expression of PKC, P-gp and MPR1(Western blot), tumor apoptosis were analyized. Results The the area of cho, lac and Lip of tumors in SW480 group were significantly higher than that in SW480/5-Fu group(P<0.05). The protein expression of PKC, P-gp and MPR1 in SW480/5-Fu group were significantly higher than that of SW480 group(P<0.05). In the TUNNEL section, apoptotic cell were observed in two groups, and there is no significant difference between two groups(P>0.05). The area of cho, lac and Lip of tumors was positively correlated with drug resistance(r, P:0.870,0.001). The the area of cho has a positive correlation with the protein expression of PKC(r, P:0.745,0.013), P-gp(r, P:0.782,0.008). Conclusion Conclusion The change of metabolites cho, lac and Lip detected with 1H- MRS has the potential to help detection of colon cancer drug resistance with MR in vivo.
引文
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[2]谢琦,张鼎旋,梁碧玲,等.1H-MRS活体检测r Ad/P53治疗人类结肠癌荷瘤裸鼠肿瘤代谢物变化[J].临床医学工程,2012,19(9):1460-1462.
[3]Xie Q,Bi-Ling Liang,Yan-Heng Wu,et al.Synergistic anticancer effect of r Ad/P53 combined with5-fluorouracil or iodized oil in the early therapeutic response of human colon cancer in vivo[J].GENE,2012,499(2):303-308.
[4]吴国昌,李伟,胡茂清,等.1H-MRS在乳腺肿瘤中的应用研究[J].中国CT和MRI杂志,2012,10(4):47-49.
[5]Beloueche-Babari M,Arunan V,Troy H,et al.Histone deacetylase inhibition increases levels of choline kinaseαand phosphocholine facilitating noninvasive imaging in human cancers[J].Cancer Res,2012,72(4):990-1000.
[6]Vaitheesvaran B,Xu J,Yee J,et al.The Warburg effect:a balance of flux analysis[J].Metabolomi cs,2015,11(4):787-796.
[7]Riemann A,Ihling A,Schneider B,et al.Impact of extracellular acidosis on intracellular p H control and cell signaling in tumor cells[J].Adv Exp Med Biol,2013,789:221-8.
[8]Elf S E,Chen J.Targeting glucose metabolism in patients with cancer[J].Cancer,2014,120(6):774-780.
[9]Zoula S,Herigault G,Ziegler A,et al.Correlation between the occurrence of 1H-MAS lipid signal,necrosis and lipid droplets during C6 rat gliomas development[J].NMR Biomed,2003,15(4):199-212.
[10]Griffin JL,Lehtimaki KK,Valonen PK,et al.Assignment of 1H NMR visible polyunsaturated fatty acids in BT4C gliomas undergoing canciclovirthymidine kinase gene therapyinduced programmed cell death[J].Cancer Res,2003,63(12):3195-3201.
[11]Kousi E,Tsougos I,Tsolaki E,et al.Spectroscopic evaluation of glioma grading at 3T:the combined role of short and long TE[J].Scientific World Journal.2012,2012(4):5461-5471.
[12]Goldman SM,Nunes TF,Melo HJ,et al.Glutamine/glutamate metabolism studied with magnetic resonance spectroscopic imaging for the characterization of adrenal nodules and masses[J].Biomed Res Int,2013(3):2013:835385-835385.