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首页> 外文期刊>Journal of experimental & clinical cancer research : >Effect of incadronate on proliferation of mesenchymal tumor cells with or without activated Ras mutation.
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Effect of incadronate on proliferation of mesenchymal tumor cells with or without activated Ras mutation.

机译:Incadronate对有或没有激活Ras突变的间充质肿瘤细胞增殖的影响。

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摘要

The present investigation examined the effect of bisphosphonates on six mesenchymal tumor cell lines and the mechanisms of inhibition of tumor cell proliferation. HT-1080, a fibrosarcoma cell line that exhibits increased Ras activity due to a mutation of the Ras gene, demonstrated significantly reduced tumor cell proliferation upon treatment with incadronate. The other cell lines, however, which lack mutation of the Ras gene, showed no influence upon treatment with incadronate. Autoradiography demonstrated no difference in the uptake of 3H-labelled incadronate between susceptible and unaffected cells. The anti-proliferation of HT-1080 was reversed by the addition of geranylgeranyl pyrophosphate. Etidronate exhibited no influence on all tested cell lines. On the basis of these data, we hypothesized that incadronate inhibits the mevalonate pathway and blocks oncogenic Ras signaling. In an effort to confirm this hypothesis, the influence of incadronate on an oncogenic Ras transfected BALB/3T3 cell line (Bhas 42) and a parental BALB/3T3 cell line were compared. The parental BALB/3T3 cells showed slight inhibition upon treatment with incadronate, however, the proliferation of Bhas 42 cells was significantly reduced. These results suggest that incadronate suppresses oncogenic Ras-activated mesenchymal tumors through the inhibition of Ras signaling pathways.
机译:本研究检查了双膦酸盐对六种间充质肿瘤细胞系的影响以及抑制肿瘤细胞增殖的机制。 HT-1080是一种纤维肉瘤细胞系,由于Ras基因的突变而具有增强的Ras活性,在用中钙酸盐处理后,肿瘤细胞的增殖明显减少。然而,其他缺少Ras基因突变的细胞系对中钙盐的治疗没有影响。放射自显影显示易感细胞和未受影响的细胞摄取3H标记的钙铝酸盐没有差异。加入香叶基香叶基香叶基焦磷酸酯可逆转HT-1080的抗增殖作用。 Etidronate对所有测试的细胞系均无影响。基于这些数据,我们假设钙内酯抑制甲羟戊酸途径并阻断致癌Ras信号传导。为了证实该假设,比较了钙铝酸盐对Ras致癌的BALB / 3T3细胞系(Bhas 42)和亲代BALB / 3T3细胞系的影响。亲代BALB / 3T3细胞在用钙铝酸盐处理后显示出轻微的抑制,但是,Bhas 42细胞的增殖显着降低。这些结果表明,茚三酮酸盐通过抑制Ras信号通路来抑制致癌的Ras活化的间充质肿瘤。

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