**3.14 Skp-2**

Skp-2 is a substrate recognition subunit of ubiquitin-protein ligase complex SCF/Skp-2, high expression of which in many tumors suggests a poor prognosis. Increased Skp-2 is believed to be associated with cell cycle disturbances in many tumors. HIV retroviral vectormediated RNAi inhibited Skp-2 high expression cells effectively by increasing the expression of p27 and p21, but it had no significant effect on Skp-2 low expression cells(Sumimoto *et al,* 2005). Intervention of Skp-2 expression in 90% A549 and H1792 lung cancer cell strains could reduce p27 expression, induce apoptosis and inhibit proliferation (Simpson *et al,* 2004). Subcutaneous injection of the adenoviral vector of Skp-2 RNAi could inhibit the growth of subcutaneously transplanted lung cancer effectively, but it was ineffective in tumors without high expression of Skp-2(Faltus *et al,* 2004). Sumimoto *et al* (Sumimoto *et al,* 2006) also found that interference with Skp-2 and BRAFD expression could inhibit the growth and invasion of melanoma cells in vitro.

### **3.15 Cytokine-induced apoptosis-inhibiting molecule**

Cell apoptosis is programmed cell death regulated by multiple genes. Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is an important regulator of cell apoptosis. It has a significant inhibitory effect on multiple links in cell apoptotic pathways and a positive regulatory effect on Ras and other survival signaling pathways, thus promoting cell survival and proliferation (Shibayama *et al,* 2004). In recent years, many studies on the relationship

Urokinase-type plasminogen activator (uPA) is an important component participating in degradation of extracellular matrix and plays an important role in invasion and metastasis of tumor cells. Super-expression of uPA receptor (uPAR or PLAUR) is detected in many malignant tumor cells. Zhou (Zhou *et al,* 2009) used a retroviral vector carrying siRNA expressing target PLAUR to treat transplanted oral squamous cell carcinoma for 30 days, and found that the mean tumor size of the intervention group was 1382mm3 versus 4181mm3 in the NS control group. The number of apoptotic cells in the intervention group was significantly greater than that in the control group (32.7 vs 2.7, P<0.01). The expression level of u-PAR, MMP2, MMP9, VEGFD, VEGFC and VEGFR-3 in the intervention group

Super-expression of P21-activated kinase 6 (encoded by PAK6) is detected in malignant prostate cancer tissues. Wen (Wen *et al,* 2009) compared the inhibitory effect of PAK6-target siRNA (by intratumor injection in transplanted pancreatic cancer tumor-bearing nude mice) and Taxol on tumors, where siRNA was injected into tumors of transplanted pancreatic cancer-bearing nude mice. The result of six-week observation showed that the mean tumor size of the control group, Taxol group, siRNA group and Taxol+siRNA group was 475mm3, 210mm, 68mm3 and 47mm3 respectively. PAK6-siRNA inhibited the growth of pancreatic cancer cells and blocked them at G2-M, demonstrating that both Taxol and PAK6-siRNA could inhibit tumor growth. The inhibitory effect of combined use of Taxol and PAK6-

Skp-2 is a substrate recognition subunit of ubiquitin-protein ligase complex SCF/Skp-2, high expression of which in many tumors suggests a poor prognosis. Increased Skp-2 is believed to be associated with cell cycle disturbances in many tumors. HIV retroviral vectormediated RNAi inhibited Skp-2 high expression cells effectively by increasing the expression of p27 and p21, but it had no significant effect on Skp-2 low expression cells(Sumimoto *et al,* 2005). Intervention of Skp-2 expression in 90% A549 and H1792 lung cancer cell strains could reduce p27 expression, induce apoptosis and inhibit proliferation (Simpson *et al,* 2004). Subcutaneous injection of the adenoviral vector of Skp-2 RNAi could inhibit the growth of subcutaneously transplanted lung cancer effectively, but it was ineffective in tumors without high expression of Skp-2(Faltus *et al,* 2004). Sumimoto *et al* (Sumimoto *et al,* 2006) also found that interference with Skp-2 and BRAFD expression could

Cell apoptosis is programmed cell death regulated by multiple genes. Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is an important regulator of cell apoptosis. It has a significant inhibitory effect on multiple links in cell apoptotic pathways and a positive regulatory effect on Ras and other survival signaling pathways, thus promoting cell survival and proliferation (Shibayama *et al,* 2004). In recent years, many studies on the relationship

decreased significantly, and proliferation-related Ki-67 was inhibited.

siRNA was significantly better than either of the two along.

inhibit the growth and invasion of melanoma cells in vitro.

**3.15 Cytokine-induced apoptosis-inhibiting molecule** 

**3.12 Urokinase-type plasminogen activator** 

**3.13 P21-activated kinase 6** 

**3.14 Skp-2** 

between CIAPIN1 and tumor formation showed that CIAPIN1 expression was increased significantly in HCC, gastric cancer and other malignant tumor tissues (Ida *et al,* 2007;Zhang *et al,* 2008). Li (Li *et al,* 2008) used adenovirus-mediated RNAi to knock out CIAPIN1 in HCC cells and found that CIAPIN1 gene expression in HCC cells was down-regulated, where cells were prevented from entering phase S and cell proliferation was inhibited. Eight weeks after injection of adenovirus/siRNA between transplanted tumor tissues, the tumor size was only one-sixth of the control group, and pathological sections showed apoptotic cells in tumor tissues.
