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[MDR-reversing effect of short peptide binding specifically to multidrug-resistant gastric cancer cells]
1State Key Laboratory of Biology and PLA Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
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.
Insights
The short peptide SY1 specifically binds to multidrug-resistant gastric cancer cells. SY1 enhances chemotherapy sensitivity and drug accumulation, offering a new approach to overcome gastric cancer drug resistance.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Context:
- Gastric cancer remains a significant global health challenge.
- Multidrug resistance (MDR) in gastric cancer limits the efficacy of conventional chemotherapy.
- Novel therapeutic strategies are needed to overcome MDR in gastric cancer.
Purpose:
- To investigate the specific binding of the short peptide SY1 to multidrug-resistant gastric cancer cells (SGC7901/VCR).
- To evaluate the effect of SY1 on reversing drug resistance in SGC7901/VCR cells.
- To assess SY1's impact on the accumulation of chemotherapeutic agents in resistant cells.
Summary:
- SY1 demonstrated specific binding to the surface of SGC7901/VCR cells, not parent SGC7901 cells.
- MTT assays revealed that SY1 significantly reduced the survival rate of SGC7901/VCR cells, enhancing sensitivity to vincristine (VCR).
- Flow cytometry confirmed that SY1 increased the intracellular accumulation of adriamycin (ADM) in SGC7901/VCR cells.
Impact:
- SY1 exhibits specific targeting capabilities for multidrug-resistant gastric cancer cells.
- SY1 shows potential in reversing drug resistance and improving the effectiveness of existing chemotherapies.
- These findings may pave the way for novel therapeutic strategies against gastric cancer MDR.
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