UNDERSTANDING THE MECHANISM OF DRUG-RESISTANT AND TUMOR RECURRENCE IN LIVER CANCER
Chemo-resistant and tumor recurrence are the major hurdle to overcome the cancer patients. Especially in hepatocellular carcinoma (HCC) is notoriously refractory to chemotherapy because of its tendency to develop multi-drug resistance (MDR), through various mechanisms. Aim: The current research is focussed on understanding the mechanism involved in chemo-resistant and tumor recurrence in liver cancer. Methods: Human hepatocellular carcinoma cell line (Huh7) was used entire study. Huh7 cells were cultured with known chemotherapeutic drugs such as 5-FU, Paclitaxel and Cisplatin-based on their Cmax concentration, and then these drug-treated cells were examined for chemoresistant and tumor recurrence properties through flow cytometry analysis, spheroid formation assay, and morphological analysis. Results: In morphological analysis confirm these all the chemo drugs were shown more cytotoxic effete than control, even though there were few viable cells noticed in cisplatin treatment. In flow cytometry analysis cisplatin pre-treated cells were well expressed LCSC marker such as CD133 and stem cell transduction factors like Oct-4 & Nanog than control. In addition to this, all the CD133 expressed cells also expressed to EpCAM. In spheroid formation assay, cisplatin pre-treated cells shown well-defined spheroid than control. Conclusion: LCSC plays a major role in chemoresistant and tumor recurrence through PI3K/Akt/mTOR, wnt-β catenin signaling, NF-kB signaling. So, targeting LCSC through EpCAM targeted therapy along with chemotherapy might be the better option for enhanced prognosis.
Keywords: LCSC, Chemoresistant, Tumor recurrence, Hepatocellular carcinoma.
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