Purpose: Hypoxia has been found to play an important role in regulating the biological characteristics of cancer stem cells (cCSCs). In this study, we tested whether a tumor hypoxic niche serves to the chemotherapeutic resistance of colon cCSCs.
Methods: Each of 23 fresh samples of human colon adenocarcinoma was transplanted into nude mice. The tumor-bearing mice randomly and equally received (A) saline, (B) 5-fluorouracil (15 mg/kg), (C) oxaliplatin (10 mg/kg), and (D) oxaliplatin plus 5-fluorouracil when xenografts reached 250 mm(3) (n = 10). After 2-week treatment, tumor cells were quantified by flow cytometry for expression of CD133 and the hypoxic proportion of CD133(+) and CD133(-) cells which were also sorted and detected for ki67 and pimonidazole via immunofluorescence.
Results: The hypoxic subpopulation of CD133(+) and CD133(-) cells was 66.5 and 26.4 %, respectively. Although there was no marked change for the hypoxic subpopulation of CD133(+) cells after treatment, the hypoxic fraction of proliferative CD133(+) cells was increased by 14.62, 16.45, and 20.46 % in groups B, C, and D, respectively. Furthermore, proliferative cells in CD133(+) and CD133(-) cells were reduced by 29.93 and 62.5 % in group C, and by 25.26 and 68.22 % in group D; in group B, however, the proliferative CD133(+) cells were increased by 37.09 %; the CD133(-) cells were unchanged.
Conclusions: Most CD133(+) cCSCs are located in a hypoxic niche, where cCSCs are better at retaining proliferating property under chemotherapy. Oxaliplatin, rather than 5-FU, inhibits proliferation of cCSCs, which may be the mechanism underlying a better outcome by oxaliplatin in colon cancer patients.