Silencing of Lysyl Oxidase Gene Expression by RNA Interference Suppresses Metastasis of Breast Cancer

Objective: The aim of this study was to investigate possible mechanisms of LOX gene effects on invasion andmetastasis of breast cancer cells by RNA interference.
Methods: LOX-RNAi-LV was designed, synthesized, andthen transfected into a breast cancer cell line (MDA-MB-231). Expression of LOX, MMP-2 and MMP-9 wasdetermined by real-time PCR, and protein expression of LOX by Western blotting. Cell migration and invasivenesswere assessed with Transwell chambers. A total of 111 cases of breast cancer tissues, cancer-adjacent normalbreast tissues, and 20 cases of benign lesion tissues were assessed by immunohistochemistry.
Results: Expressionof LOX mRNA and protein was suppressed, and the expression of MMP-2 and MMP-9 was significantly lowerin the RNAi group than the control group (P<0.05), after LOX-RNAi-LV was transfection into MDA-MB-231cells. Migration and invasion abilities were obviously inhibited. The expression of LOX protein in breast cancer,cancer-adjacent normal breast tissues and benign breast tumor were 48.6% (54/111), 26.1% (29/111), 20.0% (4/20),respectively, associations being noted with clinical stage, lymph node metastasis, tumor size and ER, PR, HER2,but not age. LOX protein was positively correlated with MMP-2 and MMP-9.
Conclusion: LOX displayed animportant role in invasion and metastasis of breast cancer by regulating MMP-2 and MMP-9 expression whichprobably exerted synergistic effects on the extracellular matrix (ECM).