In recent years, stem cell research has continued to benefit from its crossover with chemistry, particularly the investigation of small molecular drugs modulating specific targets to regulate stem cell fate. Idebenone (IDB) is a yellow crystalline powder that is used in the treatment of chronic cerebrovascular diseases. The objective of the present study was to examine whether IDB had an influence on bone marrow‑derived mesenchymal stem cells (BMSCs) extracted from the bone marrow of Sprague‑Dawley rats. The effects of IDB on cell proliferation, cell cloning and migration were investigated. Cell cycle, apoptosis, DAPI nuclear staining and senescence‑associated β‑galactosidase (SA‑β‑gal) staining were also examined. The results revealed that IDB at suitable concentrations enhanced cell cloning capacity, promoted the proliferation of BMSCs, delayed cellular senescence, and inhibited cell apoptosis and migration. Western blot analysis indicated that IDB increased the expression of B‑cell lymphoma 2 (Bcl‑2), signal transducer and activator of transcription‑3, Nanog, octamer‑binding transcription factor 4, E‑cadherin, proliferating cell nuclear antigen, cyclinD1 and cyclinD3, and decreased the expression of Bcl‑2‑associated X protein, cleaved caspase‑3, N‑cadherin, vimentin and α‑smooth muscle actin. In conclusion, these experiments confirmed that IDB in low doses had no toxic effect and may exert protective effects on BMSCs.

目的:探讨6-磷酸果糖激酶-2/果糖-2,6-二磷酸酶同工酶3(6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases 3 isozyme,PFKFB3)在结直肠腺癌中的表达及其意义.方法:选取31例结直肠腺癌患者手术切除的癌组织及其对应的癌旁组织标本,采用实时荧光定量PCR(qRT-PCR)法检测PFKFB3 mRNA表达,免疫组织化学法检测PFKFB3蛋白的表达,并探讨免疫组化阳性表达率与临床病理参数间的关系.结果:qRT-PCR结果显示,31例结直肠腺癌组织PFKFB3基因的相对表达量为1.93±1.73,明显高于其相对应的癌旁组织,差异有统计学意义(t=-2.985,P<0.01).免疫组织化学结果显示,结直肠腺癌组织及其对应的癌旁组织PFKFB3阳性表达率分别为61.3%(19/31)和3.2%(1/31),差异有统计学意义(P<0.01).PFKFB3的高表达与肿瘤直径、分化程度、侵袭、转移及治疗前癌胚抗原水平有关(均P<0.05).结论:PFKFB3对结直肠腺癌具有潜在的临床诊断价值,且与肿瘤的恶性程度存在一定的相关关系.

Studies have demonstrated low expression of miR-145 associated with cell proliferation and migration in a wide variety of tumors. Here, we studied the expression of miR-145 in relation to the occurrence and development of breast cancer. Total RNA from breast cancer tissue and corresponding adjacent normal tissue was extracted and used to detect miR-145 expression by quantitative real-time polymerase chain reaction (qRT-PCR). We also transfected breast cancer cells with hsa-miR-145 mimics, hsa-miR-145 inhibitor, mimics negative control (mimics NC) or inhibitor negative control (inhibitor NC). Cell proliferation was analyzed by colony formation assays and methyl thiazolyl tetrazolium assays. Cell proliferation in breast cancer cells was decreased after overexpression of miR-145 and increased following miR-145 suppression. Cell migration and invasion were assessed using Transwell and wound healing assays, respectively, and were also decreased after overexpression of miR-145 and increased after miR-145 suppression in breast cancer cells. Finally, western blot assays showed that overexpression of miR-145 inhibited expression of transforming growth factor-β1 (TGF-β1). Collectively, these data suggest that miR-145 may inhibit TGF-β1 protein expression which may in turn contribute to tumor formation.

Cigarette smoking is a well-known risk factor in the development and progression of malignant diseases. Nicotine, the major constituent in cigarette smoke, has also shown negative effects on stem cells. Mesenchymal stem cells (MSCs) have been widely demonstrated to migrate into tumors and play key roles in cancer progression. However, the mechanisms by which nicotine impacts MSCs and tumorigenesis of lung cancer are still undetermined. In this study we investigated the effects of nicotine on human umbilical cord mesenchymal stem cells (hUC-MSCs) and the impacts of nicotine-treated hUC-MSCs on tumor formation and progression. We found that nicotine has a toxic effect on hUC-MSCs and changes the morphology, inhibits proliferation and promotes apoptosis of hUC-MSCs in a dose-dependent manner. Nicotine-treated hUC-MSCs produce higher level of IL-6. Moreover, nicotine promotes migration, stemness and epithelial-mesenchymal transition (EMT) of hUC-MSCs by inhibiting E-cadherin expression and upregulating mesenchymal markers such as N-cadherin and Vimentin, leading to the induction of stem cell markers Sox2, Nanog, Sall4, Oct4 and CD44. Migration and proliferation of non-small cell lung cancer A549 cells and breast cancer MCF-7 cells are promoted after their coculture with nicotine-treated hUC-MSCs in a cell-cell contact-independent manner. Furthermore, nicotine-treated hUC-MSCs promote tumor formation and growth of A549 cells in nude mice. These studies demonstrated that the enhanced stemness and EMT of hUC-MSCs induced by nicotine are critical for the development of tobacco-related cancers.