الفهرس | Only 14 pages are availabe for public view |
Abstract Hepatocellular carcinoma (HCC) is one of the most common types of cancer. The high mortality and short survival time of HCC causes a serious worldwide health burden. Chemotherapy as 5-Flourouracil (5-FU) is used as the first-choice treatment for HCC, however it is associated with resistance, low efficacy and has side effects. Consequently, the administration of mesenchymal stem cells (MSCs) as a novel therapy for HCC holds great promise. MSCs can differentiate into hepatocytes, reduce liver inflammation, promote hepatic regeneration and secrete protective cytokines. This study was performed to throw more lights on the effect of MSCs alone or combined with 5FU on HCC. MSCs were isolated and cultured for usage in HCC treatment. HCC was induced in rats by using diethylnitrosamine (DENA). Animals were randomly divided into five groups as follows: group (1): control group. group (2): HCC group. group (3): 5FU treated group. group (4): BM-MSCs treated group. group (5): 5FU + BM-MSCs treated group. The effect of treatments was evaluated by biochemical, tumor markers, macroscopical, and histopathological analysis. Also, cell cycle, apoptosis assay, KI67 and CD95 were performed by flowcytometry. Results showed that administration of MSCs together with 5-FU yields a decrease in the liver enzymes with down-regulation of tumor markers as well as improvement of histopathological picture. In addition, it decreased cell proliferation. Also, MSCs did not mediate the apoptosis pathway together with reduction of CD95 expression and cell cycle arrest at G0/G1 phase. In conclusion, MSCs exerts antitumor effects by inhibiting cell proliferation, modulating the cell cycle in G0/G1 phase. It also improved the toxic effect of 5FU via improvement of liver enzymes and decreased tumor markers. The histopathological picture showed minimal reversible liver cell damage. |