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鳄鱼白细胞肽来源的KT2肽对人HCT116结肠癌异种移植瘤的抗肿瘤能力

Antitumor Ability of KT2 Peptide Derived from Leukocyte Peptide of Crocodile Against Human HCT116 Colon Cancer Xenografts.

作者信息

Maraming Pornsuda, Maijaroen Surachai, Klaynongsruang Sompong, Boonsiri Patcharee, Daduang Sakda, Chung Jing-Gung, Daduang Jureerut

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), Department of Biochemistry, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand.

出版信息

In Vivo. 2018 Sep-Oct;32(5):1137-1144. doi: 10.21873/invivo.11356.

Abstract

BACKGROUND/AIM: Many antimicrobial peptides have been shown to have anticancer activity against human cancer cell lines. Cationic KT2 peptide, derived from white blood cell extract of Crocodylus siamensis has antibacterial activity and antitumor activity against human cervical cancer cells, but there are no data on the effect of KT2 peptide on tumor growth in vivo. The anticancer activity of KT2 peptide on human colon cancer xenografts was investigated in nude mice.

MATERIALS AND METHODS

Tumors in nude mice (BALB/c -nu/nu mice) were induced by subcutaneous injection with HCT116 cells. Twelve days after cancer cell xenograft, mice were treated by intratumoral injection with phosphate-buffered saline or KT2 peptide (25 and 50 mg/kg) once every 2 days for a total of four times and mice were sacrificed at 2 days after the last treatment.

RESULTS

KT2 peptide treatment did not lead to significant difference in mouse body weight among groups, but reduced both tumor volume and weight of colon cancer xenografts. Moreover, KT2 peptide increased the expression of apoptotic proteins, such as BCL2-associated X (BAX), cleaved caspase-3, and poly (ADP-ribose) polymerase and reduced that of BCL2 apoptosis regulator in xenograft tumors.

CONCLUSION

This finding suggests that KT2 peptide may inhibit tumor growth via apoptosis induction in this mouse model and supports the antitumor ability of KT2 peptide.

摘要

背景/目的:许多抗菌肽已被证明对人类癌细胞系具有抗癌活性。源自暹罗鳄白细胞提取物的阳离子KT2肽具有抗菌活性以及对人宫颈癌细胞的抗肿瘤活性,但尚无关于KT2肽对体内肿瘤生长影响的数据。在裸鼠中研究了KT2肽对人结肠癌异种移植瘤的抗癌活性。

材料与方法

通过皮下注射HCT116细胞在裸鼠(BALB/c -nu/nu小鼠)中诱导肿瘤。癌细胞异种移植12天后,小鼠每2天接受一次瘤内注射磷酸盐缓冲盐水或KT2肽(25和50mg/kg),共注射4次,并在最后一次治疗后2天处死小鼠。

结果

KT2肽治疗在各实验组小鼠体重方面未导致显著差异,但减小了结肠癌异种移植瘤的体积和重量。此外,KT2肽增加了异种移植瘤中凋亡蛋白的表达,如BCL2相关X蛋白(BAX)、裂解的半胱天冬酶-3和聚(ADP-核糖)聚合酶,并降低了凋亡调节蛋白BCL2的表达。

结论

这一发现表明,在该小鼠模型中,KT2肽可能通过诱导凋亡来抑制肿瘤生长,并支持了KT2肽的抗肿瘤能力。

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