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Archive > Volume 22 Issue 4 > 2015,22(4):443-447. DOI:10.3872/j.issn.1007-385X.2015.04.006 Prev Next
Basic Research
The effect of cisplatin or paclitaxel on the activity of CIK cells to kill lung cancer A549 cells and its possible mechanism
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Abstract:
Objective:To study the effect of cisplatin and paclitaxel on the cytotoxic activity of cytokine-induced killer (CIK) cells toward human lung adenocarcinoma cell A549 and further explore the possible molecular mechanism involved. Methods: The IC50 of cisplatin and paclitaxel in inhibiting A549 cells were measured by using MTT assay. Cytotoxicity of CIK cells toward A549 cells that were pre-cultured with cisplatin or paclitaxel was measured through LDH releasing assay. The expression of NKG2D ligands (MICA, MICB, ULBP1, ULBP2, ULBP3) on A549 cells were analyzed by flow cytometry. The level of DNA damage response genes (ATM, ATR, CHK1, CHK2, P53) were assessed by fluorescent quantitative PCR.Results: The IC50 of cisplatin and paclitaxel in inhibiting A594 were 70 μg/ml and 39 μg/ml respectively. Cytotoxicity of CIK cells against A549 cells was significantly increased after the cells were pre-treatment with cisplatin (70 μg/ml) or paclitaxel (39 μg/ml) (P<0.05). Expression of MICA, MICB, ULBP2, and ULBP3 on A549 cells was significantly increased by the cisplatin or paclitaxel pretreatment (P<0.05), where as the level of ULBP1 was decreased after the expose (P<0.05). Furthermore, ATM expression in A594 cells was decreasedby cisplatin treatment \[(3.23±1.62)×10-6 vs (5.49±3.91)×10-8，P<0.05\], whereas the level of P53 mRNA elevated significantly after treatmentwith paclitaxel \[(14.90±5.49)×10-6vs (3.68±2.82)×10-6，P<0.05\]. Conclusion: The results indicated that cisplatinand or paclitaxel can enhance the cytotoxic activity of CIK cells toward lung cancer cells. It is conceivable that they activate DNA-damage response genes, which in turnupregulate the expression of NKG2D ligands that make cells more susceptible to CIK cells.
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Project Supported:
Project supported by Science and Technology Leading Talents Program of Zhengzhou City (No.121PLJRC532)
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