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标题：Magnesium Absorption in Intestinal Cells: Evidence of Cross-Talk between EGF and TRPM6 and Novel Implications for Cetuximab Therapy
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作者：Giuseppe Pietropaolo ; Daniela Pugliese ; Alessandro Armuzzi 等
期刊名称：Nutrients
电子版ISSN：2072-6643
出版年度：2020
卷号：12
期号：11
页码：3277-3287
DOI：10.3390/nu12113277
出版社：MDPI Publishing
摘要：Hypomagnesemia is very commonly observed in cancer patients, most frequently in association with therapy with cetuximab (CTX), a monoclonal antibody targeting the epithelial growth factor receptor (EGFR). CTX-induced hypomagnesemia has been ascribed to renal magnesium (Mg) wasting. Here, we sought to clarify whether CTX may also influence intestinal Mg absorption and if Mg supplementation may interfere with CTX activity. We used human colon carcinoma CaCo-2 cells as an in vitro model to study the mechanisms underlying Mg transport and CTX activity. Our findings demonstrate that TRPM6 is the key channel that mediates Mg influx in intestinal cells and that EGF stimulates such influx; consequently, CTX downregulates TRPM6-mediated Mg influx by interfering with EGF signaling. Moreover, we show that Mg supplementation does not modify either the CTX IC50 or CTX-dependent inhibition of ERK1/2 phosphorylation. Our results suggest that reduced Mg absorption in the intestine may contribute to the severe hypomagnesemia that occurs in CTX-treated patients, and Mg supplementation may represent a safe and effective nutritional intervention to restore Mg status without impairing the CTX efficacy.
关键词：biomarker; colorectal cancer; EGFR; hypomagnesemia; magnesium supplementation; monoclonal antibodies; targeted therapy biomarker ; colorectal cancer ; EGFR ; hypomagnesemia ; magnesium supplementation ; monoclonal antibodies ; targeted therapy