Effects of microplastics on chemo-resistance and tumorigenesis of colorectal cancer

Abstract

Microplastics (MPs) are widely distributed environmental pollutants around the world. Although studies have demonstrated that MPs have adverse effects on human health, the relationship between MPs and tumors remains unclear. The gut is the main site of microplastics absorption, and the function of MPs in the chemoresistance and progression of colorectal cancer (CRC) needs more investigation. Here, we show that MPs exist in human CRC tissues for the first time by using a laser direct infrared chemical imaging system. MPs can cause an increase in CRC incidence in animal models and promote resistance to oxaliplatin. It is illustrated that the uptake of MPs enhances levels of autophagy by activating the mTOR pathway. MPs can also promote the disorder of intestinal flora and intestinal inflammation, serving as an essential component in the onset and advancement of CRC. These results indicated that microplastic pollutants in colorectal cancer could mediate protective autophagy through the mTOR/ULK1 axis, which is one of the new reasons for chemo-resistance in CRC under the background of increasingly serious microplastics pollution. This study identified the adverse effects of MPs on colorectal cancer progression and chemotherapy prognosis, and attempted to block the intake of MPs to propose a novel approach for clinical precision treatment.

Keywords: Autophagy; CRC; Intestinal microenvironment; Microplastics; Oxaliplatin Resistance.