Abstract
Abstract
Background: Hepatocellular carcinoma (HCC) is a highly lethal disease with a limited response to chemotherapy. Understanding the molecular mechanisms and drug resistance in HCC is crucial for developing effective therapeutic strategies. This study focuses on two widely used HCC cell lines, HepG2 and SNU-449, to investigate the combination treatment of paclitaxel (PTX) and thymoquinone (TQ). PTXis a potent chemotherapeutic agent that stabilizes microtubule structure and induces cell cycle arrest, but resistance remains challenging. TQ has shown promising anticancer effects.
Methods: The antitumor effects of mono- and combined drug treatments were assessed in HepG2 and SNU-449 cell lines, including cell viability, cell cycle arrest, and apoptosis.
Results: The combination treatment synergistically enhanced the antitumor effects of PTX and TQ. It significantly reduced viable cell numbers, increased caspase-3 activation, and elevated annexin V staining. Interestingly, the combination induced differential cell cycle arrest patterns, with HepG2 cells shifting to the S phase and SNU-449cells showing an increased G2/M cell population. PTX alone induced apoptosis in both cell lines, and TQ exhibited a similar apoptotic effect. The combined treatment further potentiated the apoptotic effect. P53, a tumor suppressor gene, was upregulated by PTX and TQ in the tested cell lines, suggesting its role in modulating the treatment response. P53knockdown enhanced the antitumor properties of PTX and TQ in both cell lines.
Conclusion: The combination therapy of TQ and PTXholds promise as a potential therapeutic regimen for HCC. P53 may have a dual role, acting as a tumor suppressor and a cell protector under stress conditions. Targeting the down-regulatory mechanisms of P53could be a valuable therapeutic approach, particularly in cancers with wild-type P53.
Publisher
Research Square Platform LLC
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