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含iRGD的衍生肽在结肠癌治疗中的抗癌活性。

Anticancer activity of derived peptide with iRGD in colon cancer therapy.

作者信息

Yaghoubi Atieh, Movaqar Aref, Asgharzadeh Fereshteh, Derakhshan Mohammad, Ghazvini Kiarash, Hasanian Seyed Mahdi, Avan Amir, Mostafapour Asma, Khazaei Majid, Soleimanpour Saman

机构信息

Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Iran J Basic Med Sci. 2023;26(7):768-776. doi: 10.22038/IJBMS.2023.68331.14913.

Abstract

OBJECTIVES

Colon cancer is well-known as a life-threatening disease. Since the current treatment modalities for this type of cancer are powerful yet face some limitations, finding novel treatments is required to achieve better outcomes with fewer side effects. Here we investigated the therapeutic potential of Azurin-p28 alone or along with iRGD (Ac-CRGDKGPDC-amide) as a tumor-penetrating peptide and 5-fluorouracil (5-FU) for colon cancer.

MATERIALS AND METHODS

Inhibitory effect of p28 with or without iRGD/5-FU was studied in CT26 and HT29, as well as the xenograft animal model of cancer. The effect of p28 alone or along with iRGD/5-FU on cell migration, apoptotic activity, and cell cycle of the cell lines was assessed. Level of the BAX and BCL2 genes, tumor suppressor genes [(p53 and collagen type-Iα1 (COL1A1), collagen type-Iα2 (COL1A2)] were assessed by quantitative RT-PCR.

RESULTS

These findings show that using p28 with or without iRGD and 5-FU raised the level of p53 and BAX but decreased BCL2, compared with control and 5-FU groups in tissues of the tumor, which result in raising the apoptosis.

CONCLUSION

It seems that p28 may be used as a new therapeutic approach in colon cancer therapy that can enhance the anti-tumor effect of 5-FU.

摘要

目的

结肠癌是一种众所周知的危及生命的疾病。由于目前针对这类癌症的治疗方法虽有效但仍存在一些局限性,因此需要寻找新的治疗方法以获得更好的疗效且副作用更少。在此,我们研究了单独使用天青蛋白 - p28或联合肿瘤穿透肽iRGD(Ac - CRGDKGPDC - 酰胺)和5 - 氟尿嘧啶(5 - FU)治疗结肠癌的潜力。

材料与方法

研究了有无iRGD/5 - FU时p28对CT26和HT29细胞以及癌症异种移植动物模型的抑制作用。评估了单独使用p28或联合iRGD/5 - FU对细胞系细胞迁移、凋亡活性和细胞周期的影响。通过定量RT - PCR评估BAX和BCL2基因、肿瘤抑制基因[(p53和I型胶原蛋白α1(COL1A1)、I型胶原蛋白α2(COL1A2)]的水平。

结果

这些发现表明,与肿瘤组织中的对照组和5 - FU组相比,单独使用或联合iRGD和5 - FU使用p28可提高p53和BAX水平,但降低BCL2水平,从而导致细胞凋亡增加。

结论

p28似乎可用作结肠癌治疗的一种新的治疗方法,可增强5 - FU的抗肿瘤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96d7/10311979/67074a78bbb0/IJBMS-26-768-g001.jpg

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