الفهرس 
Abstract
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Abstract
Compared to monotherapy, combined therapy, which contains the use of two or more drugs, has shown significant enhancement in cancer treatment, with additive or synergistic effects. The consequences of mono- and combined treatment with PTX and TQ, a phytochemical compound extracted from Nigella sativa, on two HCC cell lines (HepG2 and SNU-449). TQ has demonstrated repeatedly anticancer potential against prostate, renal, skin, pancreatic, colon, cervical, breast, leukemia, and hepatic malignancies. We showed that PTX-TQ combined treatment is significantly more effective than PTX single treatment in reducing HCC cell viability, cell cycle arrest, and apoptosis. Our findings also suggested that knocking down P53 might make HCC cells more susceptible to PTX and TQ mono- and combined treatments. The combined treatment increased the potency of both drugs in decreasing the number of viable cells, triggering caspase-3, and increased annexin V stain positivity in the treated cells, In HepG2 cells, PTX with TQ differentially shifted cell cycle arrest to the S phase (p < 0.01), while in SNU-449 cells, it significantly increased the G2/M cell population (p< 0.001). In HepG2 (p <0.001) and SNU-449 cells (p< 0.001), PTX alone produced apoptosis, but TQ had a similar apoptotic effect to PTX on HepG2 (p <0.001) and SNU-449 cells (p <0.001). In HepG2 and SNU-449
Summary
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cells, the combination therapy potentiated the apoptotic effect and elevated the apoptotic rate from 52.8% (p< 0.001) to 64% (p< 0.001). Hence P53, a tumour suppressor gene, expression was upregulated by PTX and/or TQ in the examined HCC cell lines, suggesting that it may play an important role in modulating HCC cells’ response to treatment. However, in HepG2 and SNU-449 cell lines, P53 knockdown enhanced the anti-tumor effects of PTX and TQ. Therefore, the effects of PTX & TQ seem to be independent of P53. TQ in combination with PTX could be a promising treatment choice for people with HCC. According to our findings, P53 might have a dual role: in addition to suppressing tumors, also it protects cells under stress. A finding that maybe help in the targeting of cancer cells with low P53 expression levels. In malignancies with wild-type P53, specific targeting of P53 down-regulatory mechanisms could be explored for therapeutic applications. Preclinical testing’s design process can be important. The effectiveness of combination therapies in influencing biological regulatory circuits, which have built-in redundancies that make them resistant to single disturbances and feedback mechanisms that enable them to adapt to environmental changes and maintain homeostasis, is one reason for its success.