Aims: Gastrointestinal cancers are a kind of deadly malignancy afflicting close to a million peoples worldwide. 5-Fluorouracil (5-Fu) is a main chemotherapeutic agent for cancer treatment. However, prolonged exposure of 5-Fu to cancer cells may cause chemoresistance and decrease the therapeutic potential of 5-Fu.
Main methods: Replication protein A (RPA) is a component of the origin recognition complex. In our study, we explored the role of RPA1 in hepatocellular carcinoma cell SMMC-7721, gastric cancer cell SGC-7901 and colorectal cancer HT-29 via lentiviral particles infection. Flow cytometry assay was used to examine the effect of RPA1 on cell proliferation, cell cycle and apoptosis. Western blot was employed to determine the role of RPA1 on Caspase 3 expression.
Key findings: Immunohistochemstry results showed that RPA1 was highly expressed in colorectal cancer tissues. Only 5-Fu or the knockdown of RPA1 suppressed cell clone formation, induced cell cycle arrest at the G1 phase and promoted cell apoptosis by regulating the protein level of Caspase 3. And the combination of the application of 5-Fu and RPA1 silencing significantly enhanced the above effects.
Significance: RPA1 serves as an oncogene during gastrointestinal cancers progression. These studies reveal a new target for gastrointestinal cancers therapy, and the combination of 5-Fu and silencing of RPA1 provides a new attractive therapeutic measure for gastrointestinal cancers.
Keywords: 5-Fluorouracil; Cell apoptosis; Colorectal cancer; Gastric cancer; Hepatocellular carcinoma; Replication protein A1.
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