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基于中医“痰”理论探讨胃癌组织间液对肿瘤的影响及通过微小RNA-21调控机制的研究

The effects of gastric cancer interstitial fluid on tumors based on traditional Chinese medicine 'phlegm' theory and the investigation on the mechanism through microRNA-21 regulation.

作者信息

Sun D-Z, Ye M, Ju D-W, Xiu L-J, Pei B, Zhang C-A, Lu Y, Jiao J-P, Zhang X, Xu J-Y, Zhao Y, Wei P-K, Yue X-Q

机构信息

Department of Traditional Chinese Medicine, Second Affiliated Hospital of Naval Medical University, Shanghai, China.

Department of Outpatient, Central War Zone General Hospital of the Chinese People's Liberation Army, Wuhan, China.

出版信息

J Physiol Pharmacol. 2021 Jun;72(3). doi: 10.26402/jpp.2021.3.07. Epub 2021 Nov 19.

Abstract

This study aimed to investigate the effects of gastric cancer interstitial fluid (GCIF) on tumors and explore the possible mechanism of Xiaotan Sanjie decoction (XTSJ) on treatment of gastric cancer from the view of regulating microRNA-21 (miR-21) expression. The GCIF was extracted and identified by measuring the levels of interleukin-8 (IL-8), intercellular adhesion molecule 1 (ICAM-1) and miR-21. The effects of GCIF on the proliferation of SGC-7901 cells and tumor growing were assessed by cell counting kit-8 (CCK-8) assay and subcutaneously transplanted tumor-bearing nude mice model, respectively. Additionally, inhibition effect of XTSJ decoction on proliferation of SGC-7901 cells intervened by GCIF were assessed in vitro and anti-cancer effect of it was further assessed using orthotopic transplanted tumor-bearing nude mice model. The concentration of SGC-7901 gastric cancer cells were dependent on the concentration of the added GCIF. After 72 hours of continuous culture, the interstitial fluid had an obvious proliferative effect on the SGC-7901 tumor cells, which was the most significant in the high concentration group. XTSJ decoction could inhibit the growth-promoting effect (P < 0.01) of GCIF on gastric cancer cells. Intervention of the GCIF might promote the growth (P < 0.05) of the subcutaneously transplanted tumors in nude mice and decrease the net weight of the tumor-bearing nude mice (P < 0.05) after tumor removal. The GCIF was able to up-regulate the expression (P < 0.001) of miR-21 in the subcutaneously transplanted tumors. XTSJ decoction could downregulate the expression (P < 0.05) of miR-21 in SGC-7901 orthotopically transplanted tumors. XTSJ decoction can inhibit the multiplicative effect of GCIF on gastric cancer cells, growth of gastric tumor and promotion effect of GCIF on tumors, probably due to the down-regulating miR-21 expression in tumor tissues.

摘要

本研究旨在探讨胃癌组织间液(GCIF)对肿瘤的影响,并从调控微小RNA-21(miR-21)表达的角度探索消痰散结方(XTSJ)治疗胃癌的可能机制。通过检测白细胞介素-8(IL-8)、细胞间黏附分子1(ICAM-1)和miR-21的水平来提取和鉴定GCIF。分别采用细胞计数试剂盒-8(CCK-8)法和皮下移植荷瘤裸鼠模型评估GCIF对SGC-7901细胞增殖和肿瘤生长的影响。此外,在体外评估XTSJ水煎剂对经GCIF干预的SGC-7901细胞增殖的抑制作用,并使用原位移植荷瘤裸鼠模型进一步评估其抗癌作用。SGC-7901胃癌细胞的浓度取决于添加的GCIF的浓度。连续培养72小时后,组织间液对SGC-7901肿瘤细胞具有明显的增殖作用,在高浓度组中最为显著。XTSJ水煎剂可抑制GCIF对胃癌细胞的促生长作用(P<0.01)。GCIF干预可能促进裸鼠皮下移植瘤的生长(P<0.05),并降低荷瘤裸鼠在肿瘤切除后的净体重(P<0.05)。GCIF能够上调皮下移植瘤中miR-21的表达(P<0.001)。XTSJ水煎剂可下调SGC-7901原位移植瘤中miR-21的表达(P<0.05)。XTSJ水煎剂可抑制GCIF对胃癌细胞的增殖作用、胃肿瘤生长以及GCIF对肿瘤的促进作用,这可能是由于其下调了肿瘤组织中miR-21的表达。

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