Objectives: To investigate the underlying mechanisms of how the basic fibroblast growth factor monoclonal antibody (bFGFmAb) attenuates cisplatin (DDP) resistance in lung cancer using A549 cells and cisplatin-resistant A549 cells (A549/DDP). Methods: Cancer cell proliferation, cell viability, and 50% inhibitory concentration (IC50) of cisplatin were assessed. Transwell assays were utilized to evaluate the invasion activity of tumor cells in response to treatment. Epithelial-to-mesenchymal transition markers and drug resistance proteins were analysed using Western blots. Results: We demonstrate that the bFGFmAb inhibits the proliferation and invasion of both A549 and A549/DDP cells. The bFGFmAb increases cisplatin sensitivity of both A549 and A549/DDP cells as evidenced by an increase in the IC50 of cisplatin in A549 and A549/DDP cells. Furthermore, bFGFmAb significantly increases the expression of E-cadherin, whilst decreasing the expression of N-cadherin and bFGF in both cell lines, thereby showing inhibition of epithelial-to-mesenchymal transition. In addition, we demonstrate that bFGFmAb significantly reduces the expression of the lung resistance protein. Conclusions: Our data suggests that the humanized bFGFmAb is a promising agent to attenuate cisplatin resistance in NSCLC. The underlying mechanism for this effect of bFGFmAb may be associated with the inhibition of epithelial-to-mesenchymal transition and reduced expression of lung resistance protein.
Background: Valproic acid (VPA) pharmacological mechanisms are related to the anti-inflammatory and anti-viral effects. VPA is a histone deacetylases inhibitor and serves a role in its immunomodulatory impacts. VPA has complex effects on immune cell's mitochondrial metabolism. The SLC5A8 transporter of short fatty acids has an active role in regulating mitochondrial metabolism. The study aimed to investigate whether SLC5A8 expresses the sex-related difference and how SLC5A8 expression depends on gonadal hormones, VPA treatment, and NKCC1 expression in rat thymocytes.
Methods: Control groups and VPA-treated gonad-intact and gonadectomized Wistar male and female rats were investigated (n = 6 in a group). The VPA 300 mg/kg/day in drinking water was given for 4 weeks. The SLC5A8 (Slc5a8 gene) and NKCC1 (Slc12a2 gene) RNA expressions were determined by the RT-PCR method.
Results: The higher Slc5a8 expression was found in the gonad-intact males than respective females (p = 0.004). VPA treatment decreased the Slc5a8 expression in gonad-intact and castrated males (p = 0.02 and p = 0.03, respectively), and increased in gonad-intact female rats compared to their control (p = 0.03). No significant difference in the Slc5a8 expression between the ovariectomized female control and VPA-treated females was determined (p > 0.05). VPA treatment alters the correlation between Slc5a8 and Slc12a2 gene expression in thymocytes of gonad-intact rats.
Conclusion: VPA effect on the Slc5a8 expression in rat thymocytes is gender- and gonadal hormone-dependent.
Baicalin (BA) is a kind of flavonoid that is isolated from Scutellaria baicalensis Georgi, which has been verified to have hepatoprotective effects in some diseases. However, the role of BA in acute hepatic injury induced by arsenic trioxide (ATO) remains unclear. The aim of this study was to investigate the protective action of BA on acute hepatic injury induced by ATO and to probe its possible mechanism. Mice were pretreated with BA (50, 100 mg/kg) by gavage. After 7 h, ATO (7.5 mg/kg) was injected intraperitoneally to induce liver injury. After 7 days of treatment, serum and hepatic specimens were collected and assayed to evaluate the hepatoprotective effect of BA. Pathological sections and the liver function index indicated that ATO caused significant liver injury. The fluorescence of reactive oxygen species and oxidative stress indicators showed that ATO also increased oxidative stress. The inflammatory markers in ATO-induced mice also increased significantly. Staining of the terminal deoxynucleotidyl transferase dUTP nick end labeling and apoptotic factor assay showed that apoptosis increased. However, with BA pretreatment, these changes were significantly weakened. In addition, BA treatment promoted the expression of proteins related to the JAK2/STAT3 signaling pathway. The results suggest that BA can ameliorate acute ATO-induced hepatic injury in mice, which is related to the inhibition of oxidative stress, thereby reducing inflammation and apoptosis. The mechanism of this protection is potentially related to the JAK2/STAT3 signaling pathway.