合用C-Raf和PKC-αmRNA为靶点的反义寡核苷酸增强对肺腺癌A549细胞体外生长的抑制作用

Combination of antisense oligodeoxynucleotides against C-raf and PKC-α mRNA enhancing inhibition on the proliferation of A549 cells in vitro

观察了靶向 C- raf m RNA ( ISIS51 32 )和PKC- α m RNA( ISIS352 1 )的反义硫代寡核苷酸合用对肺腺癌 A549细胞体外增殖的抑制作用 ( MTT法 ) .单用药组药物浓度为 50 0 ,2 0 0和 80 nmol·L-1;合用组 A两药浓度分别为 2 50 ,1 0 0及 40 nmol· L-1,即两药药量减半 ,药物摩尔浓度之和与单用药相同 .合用组 B两药浓度分别为 50 0 ,2 0 0及 80nmol·L-1,但作用时间减半 (各 3h) ,两药作用时间之和与单用药相同 .结果表明 ,在合用组 A,两药浓度水平为 1 0 0 nmol· L-1时 ,对 A549细胞生长的抑制作用大于 ISIS352 1单用药组的 2 0 0 nmol· L-1水平 ( P<0 .0 1 ) ;在合用组 B,两药浓度水平为 2 0 0和 80 nmol· L-1时 ,对 A549细胞生长的抑制作用分别大于 ISIS352 1单用药组的 2 0 0 nmol· L-1和ISIS51 32单用药组的 80 nmol· L-1水平 ( P<0 .0 1 ) ;其余合用组各个药物浓度水平的效应 ,与相应的单用药组的效应相近 .提示靶向不同癌基因的反义药物合用 ,可能增强对肿瘤细胞的抑制作用 .

The inhibitory effects on the proliferation of lung adenocarcinoma A549 cells after being treated with combination of two antisense phosphorothiate oligodeoxynu cleotides targeted against C raf mRNA(ISIS5132) and PKC α mRNA (ISIS3521) were evaluated in this paper. The concentration of any single drug group was 500, 200 and 80 nmol·L -1 . In combination group A, the concentration of each drug was 250, 100 and 40 nmol·L -1 , whose sum of molecular concentration of two drugs was equal to single drug group. The concentration of two antisense drugs in group B were 500, 200 and 80 nmol·L -1 , respectively, whose sum of exposure time of two drugs (3 h per drug) was equal to single drug group(6 h). The results indicated as follows: the level of 100 nmol·L -1 of two drugs in combination group A was greater than that of 200 nmol·L -1 in single ISIS3521 group on the inhibition of growth of A549 cells(P<0.01). The that of 200 and 80 nmol·L -1 of two drugs in combination group B was greater than that of 200 nmol·L -1 in single ISIS3521 group and 80 nmol·L -1 in single ISIS5132 group, respectively(P<0.01). The effects of combination of two drugs in other combination groups were similar to that of the corresponding drug in single drug group on the inhibition of proliferation of A549 cells. It suggests that combination of antisense drugs directed to different target genes enhance inhibitory effects on the proliferation of cancer cells.