近日,，來(lái)自美國(guó)梅奧診所的研究者通過(guò)研究揭示了一種強(qiáng)有力的治療兩種致命性癌癥-三陰性乳腺癌和腎透明細(xì)胞癌（常見的腎癌）的方法。相關(guān)研究成果刊登在了國(guó)際雜志Molecular Cancer Therapeutics上,，文章中,，研究者報(bào)道了兩種藥物，羅咪酯肽和地西他濱,，兩種藥物可以協(xié)作來(lái)激活腫瘤抑制基因抑制腫瘤發(fā)生,。用藥后，腫瘤抑制基因會(huì)分泌卷曲相關(guān)蛋白sFRP1,，隨后腫瘤細(xì)胞便會(huì)停止生長(zhǎng),，并且死亡。
羅咪酯肽和地西他濱兩種藥物得到了FDA批準(zhǔn),，用于治療血癌和檢測(cè)固體癌癥,。研究者Copland博士表示，我們目前臨床試驗(yàn)的技術(shù)來(lái)證明這兩種藥物抗擊癌癥的效果,。sFRP1在結(jié)腸癌,、肺癌和肝癌中是無(wú)效的。研究者和其同事早期研究中發(fā)現(xiàn)sFRP1在特定的腫瘤中是沉默的,，新的研究工作揭示了其表達(dá)可以羅咪酯肽和地西他濱恢復(fù),，羅咪酯肽是一種組蛋白脫乙酰基酶抑制劑，而地西他濱是一種甲基轉(zhuǎn)移酶抑制劑,。兩種藥物可以以特定方式修飾基因來(lái)影響其表達(dá)與否,。
單獨(dú)來(lái)講，每種藥物并不能又到任何形式的癌細(xì)胞死亡,，但是實(shí)驗(yàn)室研究揭示,，如果兩種藥物聯(lián)合作用卻可以殺死腎癌和三陰性乳腺癌，這兩種癌癥每年在美國(guó)會(huì)影響超過(guò)80,，000人的健康,。如今這種藥物結(jié)合療法對(duì)于癌癥病人的治療無(wú)疑是一種希望。而且研究者表示,，也可通過(guò)活檢技術(shù)來(lái)分辨出腫瘤患者中是否有sFRP1功能的缺失,。這項(xiàng)研究由美國(guó)國(guó)立衛(wèi)生研究院支持。（生物谷Bioon.com）
編譯自：Drug Duo Turns On Cancer-Fighting Gene in Kidney, Breast Cancers
doi:10.1158/1535-7163.MCT-11-0873
PMC:
PMID:
Re-expression of tumor suppressor, sFRP1, leads to antitumor synergy of combined HDAC and methyltransferase inhibitors in chemoresistant cancers.
Simon J Cooper1, Christina A Von Roemeling2, Kylie H Kang3, Laura A Marlow2, Stefan KG Grebe4, Michael E Menefee5, Han W Tun6, Gerardo Colon-Otero7, Edith A. Perez7, and John A Copland8,*
Metastatic solid tumors are aggressive and mostly drug resistant leading to few treatment options and poor prognosis as seen with clear cell renal cell carcinoma (ccRCC) and triple negative breast cancer (TNBC). Therefore the identification of new therapeutic regimes for the treatment of metastatic disease is desirable. ccRCC and TNBC cell lines were treated with the HDAC inhibitor romidepsin and the methyltransferase inhibitor decitabine, two epigenetic modifying drugs approved by the FDA for the treatment of various hematologic malignancies. Cell proliferation analysis, flow cytometry, quantitative PCR and immuno-blotting techniques were utilized to evaluate the antitumor synergy of this drug combination and identify the re-expression of epigenetically silenced tumor suppressor genes. Combinatorial treatment of metastatic TNBC and stage 4 ccRCC cell lines with romidepsin/decitabine leads to synergistic inhibition of cell growth and induction of apoptosis above levels of individual drug treatments alone. Synergistic re-expression of the tumor suppressor gene secreted frizzled-related protein one (sFRP1) was observed in combinatorial drug treated groups. Silencing sFRP1 (shRNA) prior to combinatorial drug treatment demonstrated that sFRP1 mediates the growth inhibitory and apoptotic activity of combined romidepsin/decitabine. Furthermore, addition of recombinant sFRP1 to ccRCC or TNBC cells inhibits cell growth in a dose-dependent manner through the induction of apoptosis identifying that epigenetic silencing of sFRP1 contributes to renal and breast cancer cell survival. Combinatorial treatment with romidepsin and decitabine in drug resistant tumors is a promising treatment strategy. Moreover, recombinant sFRP1 may be a novel therapeutic strategy for cancers with suppressed sFRP1 expression.
