Specific inhibition of tumor cells by oncogenic EGFR specific silencing by RNA interference.

Specific inhibition of tumor cells by oncogenic EGFR specific silencing by RNA interference.
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DOI:
10.1371/journal.pone.0073214
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Hohjoh H
Hohjoh H
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Takahashi M;Chiyo T;Okada T;Hohjoh H

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对正常细胞和组织影响最小的抗癌药物是理想的抗癌药物。在这里,我们通过体内和体外的致癌等位基因特异性RNA干扰(RNAi)显示了对携带表皮生长因子受体(EGFR)基因致癌突变的人类癌细胞的特异性抑制。等位基因特异性RNAi(ASP-RNAi)治疗不影响无致癌等位基因的正常细胞或组织,而传统的体内RNAi抑制正常的EGFR等位基因会产生不良影响,即正常的EGFR是至关重要的。综上所述,我们目前的发现表明,在不影响正常EGFR等位基因的情况下,特异性抑制致癌EGFR等位基因可能为癌症患者提供一种安全的治疗方法,而ASP-RNAi治疗可能成为一种安全有效的抗癌治疗方法。
Anticancer agents that have minimal effects on normal cells and tissues are ideal cancer drugs. Here, we show specific inhibition of human cancer cells carrying oncogenic mutations in the epidermal growth factor receptor (EGFR) gene by means of oncogenic allele-specific RNA interference (RNAi), both in vivo and in vitro. The allele-specific RNAi (ASP-RNAi) treatment did not affect normal cells or tissues that had no target oncogenic allele, whereas the suppression of a normal EGFR allele by a conventional in vivo RNAi caused adverse effects, i.e., normal EGFR is vital. Taken together, our current findings suggest that specific inhibition of oncogenic EGFR alleles without affecting the normal EGFR allele may provide a safe treatment approach for cancer patients and that ASP-RNAi treatment may be capable of becoming a safe and effective, anticancer treatment method.
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