Leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5) is a colorectal cancer (CRC) stem cell marker. The role of Lgr5-expressing stem cells in resistance to chemotherapy is controversial. The notion that Lgr5-expressing cells are more chemotherapy resistant is supported by some data; other data do not support this notion. We hypothesized that Lgr5-expressing cells would be more chemotherapy sensitive, as Lgr5 is usually a marker of dividing cells. We tested this hypothesis by exploiting two natural variants of SW480 CRC cells: the less-differentiated Lgr5-expressing floating fraction and the more-differentiated Lgr5-depleted attached fraction. We estimated chemotherapy sensitivity using an XTT Cell Proliferation Assay Kit. We confirmed that the detected chemotherapy sensitivity differences were Lgr5-driven by overexpressing Lgr5. SW480 CRC cells that naturally express Lgr5 are those that are floating, and they are more sensitive to the chemotherapeutic compounds irinotecan (maximum difference approximately two times, 0.0001
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