IL-2和α-IFN逆转人肺腺癌细胞A549/CDDP耐药性的研究

Study on reversal of multidrug resistance of human lung adenocarcinoma cell line by interleukin 2 and interferon

目的观察人重组白细胞介素2(IL-2)和α-干扰素(α-IFN)对人肺腺癌细胞A549/顺铂(CDDP)多药耐药(MDR)的逆转作用,并探讨其机制。方法四氮甲唑兰比色法(MTT法)检测IL-2、α-IFN及IL-2+α-IFN处理前后A549/CDDP细胞对药物CDDP的敏感性。荧光分光光度法测定IL-2、α-IFN及IL-2+α-IFN处理前后A549/CDDP细胞内罗丹明聚集量。流式细胞仪检测处理前后A549/CDDP细胞P-糖蛋白(P-gp)的表达。结果经IL-2、α-IFN及IL-2+α-IFN处理48h后:①化疗药物CDDP对A549/CDDP细胞的半数抑制浓度(IC50)依次是(1.75±0.18),(2.95±0.30),(0.45±0.06),同对照组(8.10±0.72)相比,差异有显著性(P<0.05),药物敏感性提高;②A549/CDDP细胞内罗丹明平均荧光强度依次为:(4.82±1.03),(4.25±1.38)(9.13±1.86),同对照组(2.38±0.26)相比,差异均有显著性(P<0.05);③A549/CDDP细胞P-gp平均荧光强度依次为(5.98±1.13),(8.90±1.59),(3.03±0.51),同对照组(15.23±2.69)相比,差异均有显著性(P<0.05)。结论IL-2、α-IFN及IL-2+α-IFN能增加A549/CDDP细胞对CDDP的敏感性,可能机制为抑制P-gp表达,增加细胞膜的通透性,最终逆转了肿瘤细胞的多药耐药性。

Objective To study the effect on reversal of muhidrug resistance in human lung adenocarcinoma cell line A549/CDDP by human recombinant IL -2 and α- IFN. Methods Lung cell line A549/CDDP of human adenoearcinoma was cuhured in vitro,and it was treated by IL - 2, α- IFN and 1L - 2 ＋ α- IFN. Drug sensitivity of IL - 2, α- IFN and IL - 2 ＋ α- IFN was detected by using MTT assay, and intracellular accumulation of Rhodamine was examined by fluorospectrophotometry. P - glycoprotein expression was examined by FCM. Results After the treatment of A549/CDDP cell llne by IL- 2, α-IFN and IL- 2 ＋ α-IFN carried out for 48 b：（1）The IC50 of CDDP to A549/CDDP cells is（ 1.75 ±0.18） , （2.95 ±0.30） and （0.45 ±0.06） respectively,and it is（8.10±0.72） in control group. Their difference is significant （ P 〈0.05）. （2） The intracellular accumulation of Rhodamine is（4.82 ± 1.03 ） , （4.25 ± 1.38） and （9.13 ±1.86） respectively, and it is （2.38 ±0.26） in control group . Their difference is significant （ P 〈 0.05 ）. （3）The P - glycoprotein expression is （5.98 ±1.13 ） , （8.90 ±1.59） and （3.03 ±0.51 ） respectively, and it is （ 15.23 ± 2.69 ） in control group. There i, significant difference （ P 〈 0.05）. Conclusion iL - 2 and α- IFN can reverse the MDR. Its possible mechanism is inhibiting the expression of P - gp and increasing the accumulation of intracelluar chemotherapeutic CDDP in A549/CDDP cells.