TGF-beta1 reverses inhibition of COX-2 with NS398 and increases invasion in prostate cancer cells.

Bone-derived transforming growth factor (TGF)-beta1 leads to tumor growth, osteoblastic lesions and more invasion. Degradation of basement membranes caused by cyclooxygenase (COX)-2 is known as a distinctive feature of invasive cells. We investigated inhibition of COX-2 with NS398 in PC-3 and LNCaP cell lines. TGF-beta1 and dmPGE2 were added in NS398 treated or untreated cells. COX-2 did not express in PC-3, after treatment with TGF-beta1, COX-2 appeared and accompanied with enhanced invasion. COX-2 expressed in LNCaP, undetectable after addition of NS398 along with decreased invasion. Addition of TGF-beta1 reversed inhibition of NS398 in both cell lines. DmPGE2 augmented invasion in both cell lines without alteration of COX-2. These results suggest that TGF-beta1 can increase invasion and reverse inhibition of COX-2 induced by NS398. We indicate that bone-derived TGF-beta1 might contribute to clinical unsatisfied effect of NSAIDs or COX-2 specific inhibitors adjuvant therapies. Our data provide a new potential therapy for fighting against prostate cancer.