背景:肺癌是一种高度流行的恶性肿瘤,由于淋巴结转移,在所有肿瘤中死亡率最高。骨髓和脐带间充质干细胞(MSCs)已证明对肺癌具有抑瘤作用。这项研究调查了DPSC裂解物对增殖的影响,凋亡,在体内和体外研究了癌细胞的迁移和侵袭。
方法:增殖,凋亡,和迁移/转移通过细胞计数试剂盒-8测定进行评估,膜联蛋白V和碘化丙啶染色,和transwell分析,分别。凋亡的表达水平-,细胞周期-,移民-,并通过qRT-PCR和Westernblot检测粘附相关的mRNA和蛋白。肿瘤标志物癌胚抗原(CEA)的水平和mRNA表达,神经元特异性烯醇化酶(NSE),采用酶联免疫吸附试验(ELISA)和qRT-PCR检测鳞状细胞癌(SCC)。最后,建立荷瘤小鼠模型,观察DPSC裂解物腹腔注射后的抑瘤作用.
结果:DPSC裂解物降低了A549细胞的活力,并诱导了肺癌细胞的凋亡。Westernblot证实Caspase-3、Bax、坏增加了,在用DPSC裂解物处理的A549细胞中,Bcl-2蛋白水平降低。此外,DPSC裂解液抑制A549细胞的迁移和侵袭;下调细胞周期的关键基因,迁移,和粘附;并显着抑制肿瘤标志物。异种移植结果显示DPSC裂解物抑制肿瘤生长并降低肿瘤重量。
结论:DPSC裂解物抑制增殖,入侵,和转移;促进肺癌细胞的凋亡;并抑制肿瘤生长-可能为肺癌治疗提供基于细胞的替代疗法。
BACKGROUND: Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro.
METHODS: The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection.
RESULTS: DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight.
CONCLUSIONS: DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment.