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鳄鱼白细胞肽 RT2 肽对裸鼠人结肠癌异种移植瘤的抗肿瘤活性。

Antitumor activity of RT2 peptide derived from crocodile leukocyte peptide on human colon cancer xenografts in nude mice.

机构信息

Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand.

Protein and Proteomics Research Center for Commercial and Industrial Purposes (ProCCI), Faculty of Science, Department of Biochemistry, Khon Kaen University, Khon Kaen, Thailand.

出版信息

Environ Toxicol. 2018 Sep;33(9):972-977. doi: 10.1002/tox.22584. Epub 2018 Jul 18.

Abstract

RT2, derived from the leukocyte peptide of Crocodylus siamensis, can kill human cervical cancer cells via apoptosis induction, but no evidence has shown in vivo. In this study, we investigated the antitumor effect of RT2 on human colon cancer xenografts in nude mice. Twenty-four mice were injected subcutaneously with human colon cancer HCT 116 cells. Eleven days after cancer cell implantation, the mice were treated with intratumoral injections of phosphate buffered saline (PBS) or RT2 (0.01, 0.1, and 1 mg/mouse) once every 2 days for a total of 5 times. The effect of a 10-day intratumoral injection of RT2 on body weight, biochemical, and hematological parameters in BALB/c mice showed no significant difference between the groups. Tumor volume showed a significant decrease only in the treatment group with RT2 (1 mg/mouse) at day 6 (P < .05), day 8 (P < .01), and day 10 (P < .01) after the first treatment. The protein expression levels of cleaved poly (ADP-ribose) polymerase (PARP), apoptosis-inducing factor (AIF), and the p53 tumor suppressor protein (p53) in xenograft tumors increased after treatment with RT2 (1 mg/mouse) compared to those in the PBS-injected group. Moreover, RT2 increased the expression of Endo G and Bcl-2 family proteins. Therefore, the peptide RT2 can inhibit tumor growth via the induction of apoptosis in an in vivo xenograft model.

摘要

RT2 源自暹罗鳄的白细胞肽,可通过诱导细胞凋亡杀死人宫颈癌细胞,但尚未有体内证据表明。在这项研究中,我们研究了 RT2 对裸鼠人结肠癌细胞异种移植的抗肿瘤作用。24 只小鼠皮下注射人结肠癌细胞 HCT 116。在癌细胞植入后 11 天,用磷酸盐缓冲盐水(PBS)或 RT2(0.01、0.1 和 1 mg/只)对小鼠进行肿瘤内注射,每 2 天一次,共 5 次。10 天的 RT2 肿瘤内注射对 BALB/c 小鼠体重、生化和血液学参数无显著影响。仅在 RT2(1 mg/只)治疗组中,肿瘤体积在第 6 天(P<.05)、第 8 天(P<.01)和第 10 天(P<.01)首次治疗后显著下降。与 PBS 注射组相比,用 RT2(1 mg/只)处理后,异种移植瘤中裂解聚(ADP-核糖)聚合酶(PARP)、凋亡诱导因子(AIF)和抑癌蛋白 p53 的蛋白表达水平增加。此外,RT2 增加了 Endo G 和 Bcl-2 家族蛋白的表达。因此,肽 RT2 可通过诱导体内异种移植模型中的细胞凋亡来抑制肿瘤生长。

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