Environmental chemical carcinogens are major factors in the induction of lung cancer, with benzo[a]pyrene (B[a]P) being one of the most widespread and highly carcinogenic among them. Although studies have reported that B[a]P exerts its carcinogenic effects by causing mutations, inducing cytotoxicity, and inhibiting DNA synthesis, the early molecular regulatory events and mechanisms involved in B[a]P-induced tumor initiation remain unclear. This study found that the MGAT3 gene was significantly downregulated in B[a]P-induced mouse lung tumorigenesis, suggesting its important tumor-suppressive function. Further investigation revealed that suppression of MGAT3 expression promoted the invasion and migration abilities of lung cancer cells, while overexpression of MGAT3 in these cells inhibited these effects. Western blot analysis also showed that MGAT3 regulated the expression of epithelial-mesenchymal transition markers, thereby affecting the motility of lung cancer cells. Xenograft assay also confirmed the inhibitory effect of MGAT3 overexpression on tumor proliferation. Analysis of lung cancer tissue expression further validated that MGAT3 is significantly downregulated in lung cancer tissues, and this decrease in expression is associated with a poor prognosis in lung cancer patients. Our research indicates that the suppression of MGAT3 expression and its downstream regulatory molecules plays a crucial role in lung cancer development induced by environmental chemical carcinogens.

Problems, such as toxic side effects and drug resistance of chemoradiotherapy, target therapy and immunotherapy accompanying the current anti-cancer treatments, have become bottlenecks limiting the clinical benefit for patients. Therefore, it is urgent to find promising anti-cancer strategies with higher efficacy and lesser side effects. Baicalein, a flavonoid component derived from the Chinese medicine scutellaria baicalensis, has been widely studied for its remarkable anti-cancer activity in multiple types of malignancies both at the molecular and cellular levels. Baicalein exerts its anti-tumor effects by inhibiting angiogenesis, invasion and migration, inducing cell apoptosis and cell cycle arrest, as well as regulating cell autophagy, metabolism, the tumor microenvironment and cancer stem cells with no obvious toxic side effects. The role of classic signaling pathways, such as PI3K/AKT/mTOR, MAPK, AMPK, Wnt/β-catenin, JAK/STAT3, MMP-2/-9, have been highlighted as the major targets for baicalein exerting its anti-malignant potential. Besides, baicalein can regulate the relevant non-coding RNAs, such as lncRNAs, miRNAs and circ-RNAs, to inhibit tumorigenesis and progression. In addition to the mentioned commonalities, baicalein shows some specific anti-tumor characteristics in some specific cancer types. Moreover, the preclinical studies of the combination of baicalein and chemoradiotherapy pave the way ahead for developing baicalein as an adjunct treatment with chemoradiotherapy. Our aim is to summary the role of baicalein in different types of cancer with its mechanisms based on in vitro and in vivo experiments, hoping providing proof for baicalein serving as an effective and safe compound for cancer treatment in clinic in the future.