CXCL8, overexpressed in colorectal cancer, enhances the resistance of colorectal cancer cells to anoikis.

Anoikis is a form of apoptosis which occurs when anchorage-dependent cells either show loss of adhesion or inappropriate adhesion. Only a few cancer cells that detach from the primary site of the tumor acquire the ability to resist anoikis and form metastasis. The mechanism underlying the resistance of colorectal cancer (CRC) cells to anoikis remains unclear. Interleukin-8 (alternatively known as CXCL8) is associated with CRC angiogenesis and progression. Here, we found that a high abundance of CXCL8 or TOPK strongly correlated with poor overall and disease-free survival of 186 patients with CRC. A combination of high CXCL8 and high TOPK expressions had the worst prognosis. We showed that CXCL8 expression was negatively correlated with anoikis in CRC cells. CXCL8 treatment enhanced the resistance of CRC cells to apoptosis, which was accompanied by the increase of TOPK, and the activation of AKT and ERK. Moreover, we demonstrated that the inhibition of either ERK or AKT by specific chemical inhibitors attenuated the CXCL8-mediated resistance to anoikis. Treatment with AKT inhibitor abolished the effects of CXCL8 on TOPK expression, suggesting that TOPK was downstream of AKT in the process of anoikis. Taken together, we demonstrated that CXCL8 is strongly implicated in the resistance of CRC cells to anoikis, and that the AKT, TOPK and ERK pathway may be a potential therapeutic target for CRC.

[Influence of preoperative chemoradiotherapy, preoperative chemotherapy, and operation on immunity function in middle or lower rectal cancer patients].

OBJECTIVE: To study the influence of preoperative chemoradiotherapy, preoperative chemotherapy, and operation alone on the cellular immunity in patients with middle or lower rectal cancer. METHODS: Ninety middle or lower rectal cancer patients were non-randomly divided into 3 equal groups: preoperative radiotherapy group, receiving conventional radiotherapy with a total dose of 30 Gy in 10 fractions completed within 2 weeks; preoperative chemoradiotherapy group, receiving 2 cycles of single-oral drug regimen (capecitabine 1000 mg/m(2) for 2 weeks as a cycle with an interval of 1 week) and then, i.e., 2 days later, receiving conventional radiotherapy as prescribed for the patients in the preoperative radiotherapy group; and operation alone group. Operation was performed on the patients of the former 2 groups 3 weeks after the completion of the relevant treatment. Blood samples were collected on the admission day, 1 day before operation, and 7 day and 1 month after operation. Flow cytometry was used to detect the levels of CD(3)(+), CD(4)(+), CD(8)(+), CD(4)(+)/CD(8)(+), and NK cells. RESULTS: There were no significant differences in the levels of CD(3)(+), CD(4)(+), CD(8)(+), CD(4)(+)/CD(8)(+), and NK cells before and after radiotherapy between the preoperative chemoradiotherapy group and preoperative chemotherapy group (all P > 0.05). 7 days after operation, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), and NK cells were degraded and the CD(8)(+) level was increased significantly (all P < 0.05) in all 3 groups. One month after operation, the levels of CD(3)(+), CD(4)(+), CD(4)(+)/CD(8)(+), and NK cells were all significantly higher and the CD(8)(+) level was significantly lower than those before operation and 7 days after operation (all P < 0.05)in all 3 groups. There were no significant differences in the T cell number and the proportions of different categories of cells at different time points in these 3 group (all P < 0.05). CONCLUSION: Preoperative chemoradiotherapy and preoperative chemotherapy have no significant impact on the cellular immune function in the patients with rectal cancer.