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Abstract
Gastric carcinoma is a refractory disease that seriously threatens human health globally. Unfortunately, its mortality is still high among common cancers. In order to develop a new type of anti-gastric cancer drug and avoid side effects of traditional chemotheray, a new drug-targeting strategy was considered in our studies. We firstly selected certain classic cytotoxic compounds such as ansamitocin P-3 (AP-3), colchicine and paclitaxel and investigated their efficacy in the suppression of gastric cancer cell growth and tumor growth. We found that these compounds displayed their potent suppressive activities. Particularly, AP-3 showed its significant tumor suppression in xenograft mouse model, and was also observed with its severe side effects. The results supported that AP-3 itself most likely was not druggable, but might be applied for drug conjugates via coupling it to a drug delivery vehicle to enhance its anti-tumor efficacy and reduce its side effects.
Keywords: Gastric carcinoma; AP-3; Drug-targeting; Cell proliferation; Cell apoptosis; Tumor growth
Received: April 12, 2021, Accepted: April 26, 2021, Published: April 30, 2021
Introduction
Gastric carcinoma is a refractory disease that seriously threatens human health worldwide. According to the GLOBOCAN estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, the global incidence and mortality of gastric cancer are 5.6% and 7.7% respectively in 2020 [1]. Genetic and environmental factors are the main factors of gastric carcinoma [2]. Genetic factors include GOLPH3 (Golgi Phosphoprotein 3) and Akt/mTOR pathway, TLR2 (toll like receptor-2), MTA2 (Metastasis Associated 1 Family Member 2) and Coronins. The main environmental factors are Helicobacter pylori (H. pylori) infection and unhealthy diet. The proliferation of H. pylori leads to a series of complex inflammation and immune responses, which eventually develops into gastric carcinoma. Long-term high intake of salted fish, sour pickled cabbage, processed meat, saturated fat, refined grains and total carbohydrates and other unhealthy eating habits can also induce gastric carcinoma.
The current therapeutic targets for gastric carcinoma are VEGFR, TKI, EGFR, HER2, PI3K-AKT-MTOR pathway, HGF-C-MET pathway, CD9 and Galectin-7. Most of the drugs available or under investigation are small molecules that usually displayed potent anti-cancer efficacy and serious side effects. Thus, targeted cancer therapy is a hot topic in the fields of anti-cancer drug development. One of the strategies is to...