Sulfasalazine synergistically enhances the inhibitory effects of imatinib against hepatocellular carcinoma (HCC) cells by targeting NFκB, BCR/ABL, and PI3K/AKT signaling pathway‐related proteins

Shamaa, Marium M.

doi:10.1002/2211-5463.13052

Cited by 5 publications

(3 citation statements)

References 47 publications

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“…Therefore, this study not only has scientific research value but also has great clinical value. The HCC cells may be resistant to molecular targeted drugs through a variety of mechanisms: (1) compensation between different signaling pathways ( 77 – 79 ); (2) epithelial–mesenchymal transition ( 80 – 82 ); (3) cancer stem cells ( 83 – 85 ); (4) PXR and other drug metabolism clearance mechanism ( 63 ); and (5) Notch pathway and other cell prosurvival and antiapoptotic mechanisms ( 38 , 86 – 88 ). This research not only expands our molecular mechanism of HCC cell resistance to molecular targeted drugs but also helps to provide new strategies for HCC treatment.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α

Liu¹,

Yang²,

Huang³

et al. 2021

Front. Oncol.

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The transcription suppressor factor FBI-1 (the factor that binds to inducer of short transcripts-1) is an important regulator of hepatocellular carcinoma (HCC). In this work, the results showed that FBI-1 promoted the Warburg effect and enhances the resistance of hepatocellular carcinoma cells to molecular targeted agents. Knockdown of FBI-1 via its small-interfering RNA (siRNA) inhibited the ATP level, lactate productions, glucose uptake or lactate dehydrogenase (LDH) activation of HCC cells. Transfection of siFBI-1 also decreased the expression of the Warburg-effect-related factors: hypoxia-inducible factor-1 alpha (HIF-1α), lactate dehydrogenase A (LDHA), or GLUT1, and the epithelial–mesenchymal transition-related factors, Vimentin or N-cadherin. The positive correlation between the expression of FBI-1 with HIF-1α, LDHA, or GLUT1 was confirmed in HCC tissues. Mechanistically, the miR-30c repressed the expression of HIF-1α by binding to the 3′-untranslated region (3′-UTR) of HIF-1α in a sequence-specific manner, and FBI-1 enhanced the expression of HIF-1α and HIF-1α pathway’s activation by repressing the expression of miR. By modulating the miR-30c/HIF-1α, FBI-1 promoted the Warburg effect or the epithelial–mesenchymal transition of HCC cells and promoted the resistance of HCC cells to molecular targeted agents.

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Section: Discussionmentioning

confidence: 99%

Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α

Liu¹,

Yang²,

Huang³

et al. 2021

Front. Oncol.

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“…Its occurrence and development involve a variety of pathophysiological processes. The process of tumor growth and metastasis can be regulated by interfering with the signaling pathway of HCC cells [ 25 – 28 ]. Many bioactive molecules in RAS system are closely related to the proliferation and invasion of HCC cells, so exploring the mechanism is of great significance for understanding the pathogenesis, prevention and treatment of HCC [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of PLC-β1/CaM signaling pathway mediated by AT1R on the occurrence and development of hepatocellular carcinoma

Liu

Wang

et al. 2021

Cancer Cell Int

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Objective To study the roles of AT1R, PLC-β1, CaM and other related signal molecules in the formation and development of hepatocellular carcinoma (HCC) and their correlation. Methods ELISA and immunohistochemistry were used to analyze the expressions of target proteins in serum and liver tissue of HCC patients, and the correlation between AT1R, PLC-β1 and CaM and postoperative survival status of patients was followed up and determined. CCK-8 method was used to screen the doses of Ang II and candesartan sensitive to HepG2 and HCCLM3 cells. Transwell experiment was used to observe the effects of different drugs on the migration and invasion activity of HCC cells. Meanwhile, flow cytometry and Western blot were used to detect the expression levels of AT1R, PLC-β1 and CaM in the cells. Then PLC-β1 siRNA was selected to transfect HCC cells, so as to further clarify the mechanism of the above signal proteins. HepG2 cells were inoculated under the hepatic capsule of mice to induce the formation of HCC in situ. Ang II and candesartan were used to stimulate HCC mice to observe the difference in liver appearance and measure the liver index. Finally, ELISA and immunofluorescence experiments were selected to analyze the levels of target proteins in mouse serum and liver tissue. Results The expression levels of target proteins in serum and liver tissue of HCC patients were significantly increased, and the postoperative survival time of patients with high expression of AT1R, PLC-β1 or CaM was obviously shortened. Ang II and candesartan could significantly promote and inhibit the motility of HCC cells, and had different effects on the levels of AT1R, PLC-β1 and CaM in cells. However, in hepatocellular carcinoma cells transfected with PLC-β1 siRNA, the intervention ability of drugs was obviously weakened. Ang II could significantly promote the formation and progression of mouse HCC, while candesartan had the opposite effect. Meanwhile, medications could affect the expressions of target proteins in mouse serum and liver tissue. Conclusion AT1R, PLC-β1 and CaM may be risk factors affecting the formation and prognosis of HCC, and the PLC-β1/CaM signaling pathway mediated by AT1R is an important way to regulate the migration and invasion activity of HCC cells.

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“…Imatinib is a tyrosine kinase inhibitor and impairs HCC cell metastasis by increasing NM23 expression (199). To improve the anti-cancer activity of imatinib against HCC, attempts have been made to combine it with other antitumor agents such as sulfasalazine and GNF-5 [200,201]. Moreover, incorporation of imatinib into lactoferrin-modified PEGylated liquid crystalline nanostructures induces apoptosis in HCC via the mitochondrial pathway [202].…”

Section: Synthetic Drugsmentioning

confidence: 99%

Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

et al. 2023

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Autophagy is an evolutionarily conserved process that plays a role in regulating homeostasis under physiological conditions. However, dysregulation of autophagy is observed in the development of human diseases, especially cancer. Autophagy has reciprocal functions in cancer and may be responsible for either survival or death. Hepatocellular carcinoma (HCC) is one of the most lethal and common malignancies of the liver, and smoking, infection, and alcohol consumption can lead to its development. Genetic mutations and alterations in molecular processes can exacerbate the progression of HCC. The function of autophagy in HCC is controversial and may be both tumor suppressive and tumor promoting. Activation of autophagy may affect apoptosis in HCC and is a regulator of proliferation and glucose metabolism. Induction of autophagy may promote tumor metastasis via induction of EMT. In addition, autophagy is a regulator of stem cell formation in HCC, and pro-survival autophagy leads to cancer cell resistance to chemotherapy and radiotherapy. Targeting autophagy impairs growth and metastasis in HCC and improves tumor cell response to therapy. Of note, a large number of signaling pathways such as STAT3, Wnt, miRNAs, lncRNAs, and circRNAs regulate autophagy in HCC. Moreover, regulation of autophagy (induction or inhibition) by antitumor agents could be suggested for effective treatment of HCC. In this paper, we comprehensively review the role and mechanisms of autophagy in HCC and discuss the potential benefit of targeting this process in the treatment of the cancer. Graphical abstract

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Sulfasalazine synergistically enhances the inhibitory effects of imatinib against hepatocellular carcinoma (HCC) cells by targeting NFκB, BCR/ABL, and PI3K/AKT signaling pathway‐related proteins

Cited by 5 publications

References 47 publications

Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α

Knockdown of FBI-1 Inhibits the Warburg Effect and Enhances the Sensitivity of Hepatocellular Carcinoma Cells to Molecular Targeted Agents via miR-3692/HIF-1α

Effect of PLC-β1/CaM signaling pathway mediated by AT1R on the occurrence and development of hepatocellular carcinoma

Targeting and regulation of autophagy in hepatocellular carcinoma: revisiting the molecular interactions and mechanisms for new therapy approaches

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