c-Ha-ras和c-myc反义寡聚脱氧核苷酸对人胃癌细胞生长增殖的影响

c-Ha-ras, c-myc antisense oligodeoxynucleotides inhibit the proliferation and.DNA synthesis in human gastric carcinoma cell lines

作者观察了人工合成的反义c-Ha-ras和 c-myc寡聚脱氧核昔酸(ASO-r,ASO-m)对两株胃癌细胞中Ha-ras癌基因表达和细胞生长增殖的影响。观察到ASO-r能显著抑制MGc-803细胞P21蛋白合成(作用12 h抑制率达48.10％,P<0.01),同时对其DNA合成和细胞增殖也有较显著的抑制作用(抑制率分别为76.79％,55.61％,P<0.05)。ASO-r对SGc-7901细胞的DNA合成和细胞增殖也有类似的抑制作用(抑制率分别为76.78％,62.02％,P<0.05)。ASO-m对两株细胞的细胞增殖和SGc-7901细胞DNA合成均无明显影响,仅对MGc-803细胞的DNA合成有抑制作用(抑制率为71.37％,P<0.05)。结果表明:ASO-r能够阻断c-Ha-ras癌基因表达,并抑制胃癌细胞生长增殖;c-Ha-ras癌基因可能是维持胃癌细胞恶性生长表型的主要因素。

The effects of two antisense oligodeoxynucleotides on the expression of c-Ha-ras proto-oncogene and the growth of human gastric carcinoma cell lines were observed. Synthetic 15-mer directed at the region of the translational initiation site of c-Ha-r<25 proto-oncogene (ASO-r) greatly inhibited the proliferation (55. 61%, P<0. 05) and DNA synthesis (76. 79%, P<0. 05) of MGc-803 cell line. It also inhibited the proliferation (62. 02% , P<0. 05) and DNA synthesis (76. 78% , P<0. 05) of SGc-7901 cell line. A reduction in intracellular P21 ras protein levels in MGc-803 cell line was observed 6 h after the treatment with ASO-r and maintained over 12 h. Another synthetic 15-mer targeted against the initiation codon and downstream 4 codons of c-myc proto-oncogene (ASO-m) just only inhibited DNA synthesis of MGc-803 cell line (71.37%, P<0. 05). Control 15-mer did not inhibit the expression of P21 protein and proliferation of these cell lines. These experiments provide evidence that ASO-r could be effective in inhibiting the expression of c-Ha-ras proto-oncogene and controlling the growth of human gastric carcinoma cells, that the over-expression of c-Ha-ras proto-oncogene may mainly be associated with the malignant proliferation of human gastric carcinoma cells.