Tumor suppressor in lung cancer 1 (TSLC1) is tightly implicated in a variety of biological processes and plays critical roles in tumor development and progression. However, the roles of TSLC1 in cutaneous squamous cell carcinoma (CSCC) remain to be unraveled. Here, we reported the TSLC1 gene that was significantly downregulated in CSCC tissues and cells, and survival times of patients with TSLC1 at a low level were markedly lower than that at a high level (P = 0.0070). A stepwise investigation demonstrated that an elevated TSLC1 level evoked obvious proliferation and invasion inhibitions and arrested cell cycle at G0/G1 phase in A431 cells. Moreover, increase of caspase-3 activity mediated by elevated TSLC1 level induced cell apoptosis in A431 cells. Most notably, upregulation of TSLC1 expression reduced the numbers of colony formation and tumorigenicity. Collectively, our results presented herein suggest that TSLC1 as tumor suppressor may play prominent roles in development and progression of CSCC via regulation of different biological processes.

A recent report showed that reversine treatment could induce murine myoblasts dedifferentiation into multipotent progenitor cells and inhibit proliferation of some tumors, and other reports showed that apoptosis of lung adenocarcinoma cells could be induced by aspirin. The aim of the present study was to evaluate the synergistic antitumor effects of reversine and aspirin on cervical cancer. The inhibition rate of reversine and aspirin on cervical cancer cell lines' (HeLa and U14) was determined by MTT method, cell cycle of HeLa and U14 cells was analyzed by FACS, mitochondrial membrane potential of HeLa and U14 was detected using a JC-1 kit. HeLa and U14 colony formation was analyzed by soft agar colony formation assay. The expression of caspase-3, Bcl-2/Bax, cyclin D1 and p21 was detected by qRT-PCR and Western Blotting. Moreover, tumor weight and tumor volume was assessed using a murine model of cervical cancer with U14 cells subcutaneously (s.c.) administered into the neck, separately or combined with drug administration via the intraperitoneal (i.p.) route. The inhibition rate of cells in the combination group (10 lmol/L reversine, 10 mmol/ L aspirin) increased significantly in comparison to that when the drugs were used alone (P \ 0.05); moreover, this combination could synergistically inhibit the proliferation of five cervical cancer cell lines (HeLa, U14, Siha, Caski and C33A). In the therapeutic mouse model, tumor weight and tumor volume of cervical cancer bearing mice was more reduced when compared with the control agents (P \ 0.05) in tumor-bearing mice. The combination of reversine and aspirin exerts synergistic growth inhibition and apoptosis induction on cervical cancers cells.

Increasing evidence has demonstrated that the tumor suppressor gene deleted in liver cancer-1 (DLC1) is tightly implicated in the development and progression of tumors and is verified to be downregulated in a variety of tumors. However, the roles and precise molecular mechanisms of DLC1 in cutaneous squamous cell carcinoma (cutaneous SCC) remain to be elucidated. In the present study, we confirmed the reduced level in cutaneous SCC tissues and cells, and DLC1 mRNA relative level in cutaneous SCC tissues with lymph node metastasis (0.801 ± 0.079) was markedly lower than those without lymph node metastasis (1.245 ± 0.071) (P < 0.0001). Importantly, the survival rates of patients with low DLC1 level were lower than those with high DLC1 level (P = 0.0051). Further investigation revealed that DLC1 overexpression inhibited proliferation and arrested cell cycle at G0/G1 phase in A431 cells, which may be tightly associated with upregulation of p21 protein and downregulation of cyclin D1 and cdk2 proteins. Moreover, the decreases of FAK and p-FAK as well as the increase of E-cadherin level mediated by elevated DLC1 level suppressed invasion in A431 cells. Additionally, DLC1 overexpression induced apoptosis coupled with elevations of Bax level and caspase-3 activity and decrease of Bcl-2 level in A431 cells. Taken altogether, our data presented herein suggest that DLC1 plays a pivotal role in the development and progression of cutaneous SCC, which may be in part achieved by regulating the signaling pathway related to proliferation, invasion, cell cycle, and apoptosis in cutaneous SCC cells.

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