Secukinumab plays a synergistic role with starvation therapy in promoting autophagic cell death of hepatocellular carcinoma via inhibiting IL-17A-increased BCL2 level.

It is known that IL-17A inhibits autophagy of hepatocellular carcinoma (HCC) cells, thus contributing to the carcinogenesis of HCC. Starvation therapy can promote the autophagic death of HCC cells by blocking the nutrition supply. The purpose of this study was to explore whether the pharmacological antagonist of IL-17A, secukinumab, and starvation therapy have a synergistic effect on the autophagic cell death of HCC. Here, it could be observed that compared with serum-free condition, the combination of secukinumab and serum-free status better promoted autophagy (observed by LC3 conversion rate, p62 protein expression and the formation of autophagosomes), and more significantly inhibited the survival and function (observed by Trypan blue staining, CCK-8, Transwell, and scratch assays) in HCC HepG2 cells. Moreover, secukinumab significantly decreased BCL2 protein expression under serum-normal and serum-free conditions. However, both the addition of recombinant IL-17A and overexpression of BCL2 blocked the regulation of secukinumab on the survival and autophagy in HepG2 cells. Nude mice experiments demonstrated that compared to the lenvatinib-alone group, the combination group of lenvatinib and secukinumab better inhibited the in vivo tumorigenesis of HepG2 cells and enhanced autophagy in xenotumor tissues. Furthermore, secukinumab significantly decreased BCL2 protein expression in xenotumor tissues without or with lenvatinib application. In conclusion, the antagonism of IL-17A with secukinumab, due to the upregulation on BCL2-related autophagic cell death, can cooperate with starvation therapy in inhibiting HCC carcinogenesis. Our data suggested that secukinumab can become an effective adjuvant for the treatment of HCC.

Ultrasound-guided bilateral erector spinae plane block in laparoscopic colon cancer surgery : A randomized controlled prospective trial.

BACKGROUND: The efficacy of erector spinae plane block (ESPB) for pain control in other surgeries remains an interesting topic of discussion. This study aimed to evaluate the safety and efficacy and quality of recovery of ultrasound-guided bilateral ESPB in laparoscopic surgery for colon cancer. MATERIAL AND METHODS: In this study 50 patients were included and randomly divided into the intervention group (E group, n = 25) and the control group (C group, n = 25). Patients in the E group received general anesthesia with preoperative bilateral ultrasound-guided ESPB, whereas patients in the C group received general anesthesia with saline injection in the erector spinae plane preoperatively. Data on intraoperative and postoperative anesthetic effects and the effect on enhanced recovery after surgery were recorded and analyzed. RESULTS: Rocuronium consumption in the intervention group was 82.80 ± 21.70 mg, which was lower than that in the control group (P < 0.05). Visual analog scale scores at 2, 6, and 24 h after surgery in the intervention group were lower than those in the control group (Fbetween = 34.034, P = 0.000). The time to ambulation, consumption of ketorolac tromethamine, time to oral intake and hospital stay after operation in the intervention group were significantly lower than those in the control group (P < 0.05). The block area at the different baselines was significant (Fbetween = 3.211, P = 0.009). The association between baseline and time was significant (Fbaseline * time = 3.268, P = 0.001). CONCLUSION: This study confirmed that ultrasound-guided ESPB technology is safe and beneficial for patients with colon cancer undergoing laparoscopic colon surgery.