State Key Laboratory of Applied Microbiology in South China (Ministry-Guangdong Province Jointly Breeding Base), and Guangdong Institute of Microbiology, Guangzhou, China.
PLoS One. 2012;7(8):e44579. doi: 10.1371/journal.pone.0044579. Epub 2012 Aug 30.
Due to an altered expression of oncogenic factors and tumor suppressors, aggressive cancer cells have an intrinsic or acquired resistance to chemotherapeutic agents. This typically contributes to cancer recurrence after chemotherapy. microRNAs are short non-coding RNAs that are involved in both cell self-renewal and cancer development. Here we report that tumor cells transfected with miR-378 acquired properties of aggressive cancer cells. Overexpression of miR-378 enhanced both cell survival and colony formation, and contributed to multiple drug resistance. Higher concentrations of chemotherapeutic drugs were needed to induce death of miR-378-transfected cells than to induce death of control cells. We found that the biologically active component isolated from Ganoderma lucidum could overcome the drug-resistance conferred by miR-378. We purified and identified the biologically active component of Ganoderma lucidum as ergosterol peroxide. We demonstrated that ergosterol peroxide produced greater activity in inducing death of miR-378 cells than the GFP cells. Lower concentrations of ergosterol peroxide were needed to induce death of the miR-378-transfected cells than in the control cells. With further clinical development, ergosterol peroxide represents a promising new reagent that can overcome the drug-resistance of tumor cells.
由于致癌因子和肿瘤抑制因子表达的改变，侵袭性癌细胞对化疗药物具有内在或获得性耐药性。这通常是化疗后癌症复发的原因。microRNAs 是短的非编码 RNA，参与细胞自我更新和癌症的发生发展。在这里，我们报告说，转染 miR-378 的肿瘤细胞获得了侵袭性癌细胞的特性。miR-378 的过表达增强了细胞的存活和集落形成能力，并导致多药耐药。需要更高浓度的化疗药物来诱导转染 miR-378 的细胞死亡，而不是诱导对照细胞死亡。我们发现，从灵芝中分离得到的生物活性成分可以克服 miR-378 赋予的耐药性。我们纯化并鉴定了灵芝的生物活性成分麦角甾醇过氧化物。我们证明麦角甾醇过氧化物在诱导 miR-378 细胞死亡方面比 GFP 细胞更有效。需要更低浓度的麦角甾醇过氧化物来诱导转染 miR-378 的细胞死亡，而不是对照细胞。随着进一步的临床开发，麦角甾醇过氧化物代表了一种有前途的新试剂，可以克服肿瘤细胞的耐药性。
