Apatinib Mesylate Can Promote the Activation of Nox4/Drp1/Nlrp3 in Aortic Tissues of Nude Mice With Gastric Cancer

Objective: Apatinib is a VEGFR-TKI for the treatment of gastric cancer. The aim of this study is to investigate whether apatinib can increase the expression of NOX4/Drp1/NLRP3 pathway in the aorta of mice with gastric cancer. Design and method: Six 5-week-old SPF male nude mice were randomly divided into tumor group (T, n=3) and tumor + apatinib treatment group (T+A, n=3). Human gastric cancer cells (MKN45) were inoculated into the armpit of mice. The T group was given normal saline 0.2 ml per day by gavage, and the T + A group was given apatinib 100mg/kg by gavage for one month. The aortic tissues of all nude mice were collected to extract protein. The protein expression levels of NOX4, Drp1, NLRP3, Caspase-1, GSDMD, IL-18, and GAPDH in aortic tissues were detected by Western blot. ImageJ was used to measure the gray value, and the gray value of the target protein /GAPDH gray value was considered as the relative expression of the target protein. Independent sample T-test was used to compare the statistical differences between the two groups using GraphPad 8.0.2. Results were expressed as mean ± standard deviation, and P < 0.05 was considered statistically significant. Results: The results showed that compared with the tumor group, The expression of NOX4 in T+A group was increased (2.320±0.2365 VS 1.718±0.1635, P = 0.0223). The expression of Drp1 in T+A group was increased (1.317±0.2160 VS 0.8216±0.2178, P= 0.0489), and the expression of NLRP3 was increased in T+A group (1.634±0.1271 VS 0.7997±0.1848, P=0.0030). The expression of Caspase-1 was increased in T+A group (1.075±0.1088 VS 0.5912±0.05073, P=0.0022). The expression of GSDMD was also increased in T+A group (0.7845±0.01213 VS 0.3443 ±0.07458, P=0.0144). Compared with the tumor group, the expression of IL-18 in the aorta of the T+A group was not significantly different (1.266±0.1236 VS 1.198 ±0.1821, P=0.6170). Conclusions: The conclusions show that Apatinib can activate the expression of NOX4/Drp1/NLRP3 pathway in the aorta of mice with gastric cancer, which may cause vascular damage by affecting oxidative stress, mitochondrial dysfunction, and inflammatory response in the aorta. Further in-depth research is needed.