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


CONCLUSIONS
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.
Wang
Peng
P
State Key Laboratory of Biology and PLA Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Ding
Jie
J
Lin
Tao
T
Han
Shuang
S
Cao
Shan-shan
SS
Ge
Fu-lin
FL
An
Guang-qun
GQ
Li
Rong
R
Lei
Ting
T
Bai
Fei-hu
FH
Fan
Dai-ming
DM
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001435:Bacteriophages / Q000235:genetics; D001665:Binding Sites; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014750:Vincristine / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D019151:Peptide Library; D010456:Peptides, Cyclic; D014750:Vincristine; D004317:Doxorubicin