الفهرس 
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Abstract
Background: Sorafenib is an FDA approved chemotherapeutic against Hepatocellular Carcinoma (HCC), yet associated with various resistance mechanisms. The role of high glucose status on sorafenib action is still to be elucidated. This study clarifies such interaction; taking HepG2 cell lines as HCC models, MALAT1 and H19 as molecular players.
Methodology: HepG2 cell lines were purchased and classified into 8 groups. High glucose status was set by using D-glucose (33mM) with insulin (1µM). Mannitol (27.5mM) was used as a negative osmotic control. Two concentrations of sorafenib were prepared; 15µM and 20µM. All experiments were carried out in triplicates. Cellular viability was assessed with MTT viability assay. Then, with trypan blue viability assay, the results were double checked and HepG2 morphology was examined by optical microscopy. MALAT1 and H19 RQs were assessed by real time PCR (RT-PCR). Statistical analysis was performed by SPSS software.
Results: In comparison with sorafenib impact on HepG2, high glucose status drops cellular viability to 83.13% (p < 0.01). Similar outcomes occur with hyperosmolar mannitol, it decreases cellular viability to 72.89% (p < 0.001). Regarding the molecular impact, hyperosmolar mannitol with sorafenib elevates both MALAT1 and H19. Yet, high glucose status elevates MALAT1 and declines H19 (p < 0.05 and p < 0.001 for MALAT1 and H19 comparisons respectively).
Conclusion: High glucose settings sensitize HepG2 to the cytotoxic impact of sorafenib and so does mannitol. This could attribute the impact of high glucose status to the hyperosmolar stress it induces on HepG2. Mannitol is recommended for further confirmatory studies either as a separate therapeutic or as an adjuvant to sorafenib.