反义寡核苷酸治疗乳腺癌研究进展(英文)

乳腺癌是一类与多基因相关的恶性肿瘤,有些痛基因如HER-2(c-erbB-2,Neu),bcl-2/6cl-xL,蛋白激酶A(PKA),运铁蛋白受体基因(TfR gene)等的过度表达对乳腺癌的预后有明显影响,有证据表明抑制上述过度表达基因能明显改善乳腺痛的治疗效果。近年,反义治疗这种能抑制特定癌基因过度表达的有效手段被应用于乳腺癌的治疗。研究表明,在多数情况下,反义寡核苷酸(ON)能在mRNA或蛋白水平抑制目的基因的表达,有些反义ON在体和离体对乳腺癌细胞系或动物乳腺癌异植肿瘤均显示出令人鼓舞的治疗效果。此外,反义ON与常规化疗药物合用也能产生协同的抗肿瘤作用。反义ON与化疗药物合用可能在不远的将来是治疗乳腺癌的最佳方法之一。

Advancements of antisense oligonucleotides in treatment of breast cancer

Breast cancer is one kind of multi-gene related malignancy.Overexpression of some oncogenes such as HER-2(c-erbB-2,Neu),bcl-2/bcl-xL,protein kinase A(PKA),and transferrin receptor gene(TfR gene),etc significantly affect the prognosis of breast cancer.It was shown that specific suppression of the overexpressed genes above resulted in the improvement of the therapy of breast cancer.Antisense interference.one of useful tools for inhibiting the overexpression of specific oncogenes,was involved in the therapy of breast cancer in recent years. Data indicated that antisense oligonucleotides(ON)could inhibit specially the expression of the target genes on mRNA or protein levels in most of cases;some ON candidates showed encouraging therapeutic effects in vitro and in vivo on breast cancer cell lines or xenografts.Furthermore,the combination use of the antisense ON and normal chemotherapeutic agents indicated synergistic antitumor effects,which was probably the best utilization of antisense ON in the treatment of breast cancer.