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[特异性结合多药耐药胃癌细胞的短肽的多药耐药逆转作用]

[MDR-reversing effect of short peptide binding specifically to multidrug-resistant gastric cancer cells].

作者信息

Wang Peng, Ding Jie, Lin Tao, Han Shuang, Cao Shan-shan, Ge Fu-lin, An Guang-qun, Li Rong, Lei Ting, Bai Fei-hu, Fan Dai-ming

机构信息

State Key Laboratory of Biology and PLA Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Zhonghua Zhong Liu Za Zhi. 2007 Apr;29(4):258-61.

Abstract

OBJECTIVE

To investigate the binding effect of the short peptide SY1 to the multidrug-resistant gastric cancer cell line SGC7901/VCR cells and its reversing effect on those cancer cells.

METHODS

The cultured cells were divided into two groups named SGC7901 and SGC7901/VCR. The SGC7901/VCR group was co-cultured with vincristine (VCR). SY1 was obtained from cyclic 7-mer peptide library by differential screening. Immunofluorescence technique was used to detect the capacity of SY1-containing positive phage specifically binding to SGC7901/VCR cells, compared with that of the negative phage and unrelated phage. MTT assay in vitro was performed to analyze the alteration of drug resistance of SGC7901/ VCR cells, using the positive phages and the chemically synthesized SY1 peptide. Flow cytometry assay was performed to detect the accumulation and retention of adriamycin (ADM) in the SGC7901/VCR cells.

RESULTS

Immunofluorescence analysis showed that the SY1-containing positive phages could bind to the SGC7901/VCR cell surface but not to its parent cell line SGC7901 cells. The unrelated phage and negative phage did not bind to SGC7901/VCR cells. These results indicated that SY1 could specifically bind to SGC7901/VCR cells. MTT assay in vitro showed that the survival rate of SGC7901/VCR cells was reduced considerably by the positive phages and the chemically synthesized SY1 peptide (P <0. 05), indicating that SY1 enhanced the sensitivity of SGC7901/VCR cells to chemotherapeutic drug VCR. Flow-cytometric detection showed that SY1 enhanced the accumulation of ADM in the SGC7901/VCR cells, compared with that of the negative phages and the unrelated phages (P <0.05).

CONCLUSION

SY1 not only is able to bind to SGC7901/VCR cells specifically, but also can partly reverse the resistance of SGC7901/VCR cell line to chemotherapeutic drug VCR. Those findings might be important to open a new approach to reverse the gastric cancer MDR.

摘要

目的

研究短肽SY1对多药耐药胃癌细胞系SGC7901/VCR细胞的结合作用及其对这些癌细胞的逆转作用。

方法

将培养的细胞分为SGC7901和SGC7901/VCR两组。SGC7901/VCR组与长春新碱(VCR)共培养。通过差异筛选从环状七肽库中获得SY1。采用免疫荧光技术检测含SY1的阳性噬菌体与SGC7901/VCR细胞特异性结合的能力,并与阴性噬菌体和无关噬菌体进行比较。使用阳性噬菌体和化学合成的SY1肽,通过体外MTT法分析SGC7901/VCR细胞耐药性的变化。采用流式细胞术检测阿霉素(ADM)在SGC7901/VCR细胞中的蓄积和滞留情况。

结果

免疫荧光分析显示,含SY1的阳性噬菌体可与SGC7901/VCR细胞表面结合,但不与其亲本细胞系SGC7901细胞结合。无关噬菌体和阴性噬菌体不与SGC7901/VCR细胞结合。这些结果表明SY1可特异性结合SGC7901/VCR细胞。体外MTT法显示,阳性噬菌体和化学合成的SY1肽可显著降低SGC7901/VCR细胞的存活率(P<0.05),表明SY1增强了SGC7901/VCR细胞对化疗药物VCR的敏感性。流式细胞术检测显示,与阴性噬菌体和无关噬菌体相比,SY1增强了ADM在SGC7901/VCR细胞中的蓄积(P<0.05)。

结论

SY1不仅能够特异性结合SGC7901/VCR细胞,还能部分逆转SGC7901/VCR细胞系对化疗药物VCR的耐药性。这些发现可能为逆转胃癌多药耐药开辟新途径具有重要意义。

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