Although ovarian cancer is heterogeneous with various histologic types, current treatment guidelines are generally the same for all histologic types. Expression of HOX genes in epithelial ovarian cancer (EOC) was known to be histology-specific. We performed a series of in vitro and in vivo studies to find out a tailored strategy of inhibiting HOXB9 expression for overcoming platinum resistance in mucinous EOC. HOXA10 and HOXB9 showed exclusively high expression in SKOV-3 and RMUG-S, respectively. HOXA10 siRNA treatment made a significant decrease in cell viability of SKOV-3, but not RMUG-S. By contrast, HOXB9 siRNA treatment made a significant decrease in cell viability of RMUG-S, but not SKOV-3. HOXA10 siRNA and HOXB9 siRNA treatments: increased the expression level of cleaved PARP and caspase-3 in SKOV-3 and RMUG-S, respectively; expression of vimentin was decreased while expression of E-cadherin was increased; SOX-2, Nanog, and Oct-4 also decreased in both cell lines after specific siRNA treatment. When injected with RMUG-Sko HOXB9 and SKOV-3oe HOXB9 in mouse models, we clearly showed that the tumors from RMUG-Sko HOXB9 grew significantly slower than those from control. By contrast, the tumors from SKOV-3oe HOXB9 grew significantly faster than those from control. After harvesting, the cells from the SKOV-3oe HOXB9 were characterized with resistance to cisplatin and higher expression of vimentin than those form the control. \r\nOur findings suggest that platinum-resistance of mucinous ovarian cancer might be defeated by inhibiting HOXB9, which could be a target of tailored strategy for overcoming the resistance to platinum in mucinous EOC.\r\n
