Hyaluronan (HA) and
hyaluronan synthases (HAS) have been implicated in
cancer growth and progression. We previously have shown that HAS3 and HA mediate
tumor growth in SW620
colon cancer cells, but the mechanism remains poorly understood. In addition, the effect of HAS3 inhibition on
tumor growth with other cells lines has not been explored. We therefore hypothesized that inhibition of HAS3 in highly tumorigenic HCT116
colon cancer cells would decrease
tumor growth and that the underlying mechanism would involve altering proliferation and/or apoptosis. HAS3 expression was inhibited by transfection with
siRNA; a scrambled sequence served as a control. Stable transfectants were injected into the flanks of nude mice and
tumor growth followed for 30 days. Proliferation and apoptosis were then assessed in the harvested
tumors. Results were compared using the Students' t-test and ANOVA where appropriate.
siRNA transfection decreased HAS3 expression,
protein production, and pericellular HA retention, and decreased in vivo
tumor growth. Proliferation was unaffected in the HCT116
tumors, but increased slightly in the SW620
tumors. In contrast, HAS3 inhibition significantly increased apoptosis in all
tumors. HAS3 inhibition decreases subcutaneous
tumor growth by
colon cancer cells and significantly increases apoptosis with less effect on proliferation. These data show that HAS3 and HA mediate
colon cancer growth by inhibiting apoptosis.