It has been reported that suppression of
protein kinase N3 (PKN3) expression in vascular and lymphatic endothelial cells results in the inhibition of
tumor progression and
lymph node metastasis formation. The present study investigated whether combination
therapy of
small interfering RNA (
siRNA) against PKN3 and
doxorubicin (DXR) could increase therapeutic efficacy against liver and lung
metastases. In vitro transfection of PKN3
siRNA into PKN3-positive MDA-MB-231, LLC, and Colon 26 cells and PKN3-negative MCF-7 cells did not inhibit cell growth and did not increase sensitivity to DXR. However, following in vivo treatment, PKN3
siRNA suppressed the growth of liver MDA-MB-231 and lung LLC and MCF-7
metastases, although combination
therapy with DXR did not increase the therapeutic efficacy. By contrast, in liver MCF-7
metastases, PKN3
siRNA or DXR alone did not exhibit significant inhibition of
tumor growth, but their combination significantly improved therapeutic efficacy. Treatment of liver MDA-MB-231
metastases with PKN3
siRNA induced a change in vasculature structure via suppression of PKN3
mRNA expression. PKN3
siRNA may induce antitumor effects in lung and liver
metastases by suppression of PKN3 expression in stroma cells, such as endothelial cells. From these findings, PKN3
siRNA alone or in combination with DXR may reduce the
tumor growth of liver and lung
metastases regardless of PKN3 expression in
tumor cells.