The Mechanism Of Multicellular Resistance Induced By NF-κB Signaling Pathway In Colon Carcinoma Cells

Background: Colon cancer constitutes a major health problem. Although novel anticancer drugs (such as CPT-11, oxaliplatin, and so on) show clear benefit for treating advanced colorectal cancer, drug resistance do impact the therapeutic effect and prognosis. It is essential to establish the dominant mechanism of resistance to chemotherapy in human tumors. This is often considered to be the so-called multidrug resistance (MDR) mechanism. Abundant work has being done on the mdr1 gene and the PgP product encoded. Unfortunately, all this effort has not yielded a useful drug. An explanation for this failure is that the experimental model used for this research was not appropriate. It has been reported that a mechanism of resistance induced in vivo might not be observed when tumor cells are cultured as monolayer in vitro. It is urgent to establish a new model for drug resistance research. This kind of resistance observed in vivo is only encountered when cells are cultured as spheroids. Tumor resistance to anticancer drugs is a real phenomenon, but the most prevalent mechanism may not correspond to MDR. Instead, the so-called multicellular resistance (MCR) could be the most important obstacle to cancer treatment. The mechanisms involved in MCR have not yet been clearly elucidated. Adhesion molecules maybe play a role in MCR, because it has been reported that E-cadherin can increase the drug resistance through regulating the cell cycle of mammary carcinoma multicellular spheroids (MCS). Most anticancer drugs induce tumor cells to apoptosis. However, tumor cells can inhibit apoptosis to escape to be killed. The NF-κB signaling pathway and the transcription factors that it activates have emerged as critical regulators of the apoptotic response. NF-κB is most commonly involved in suppressing apoptosis by transactivating the expression of antiapoptotic genes. However, whether NF-κB signaling pathway is implicated in MCR is not clear nowadays. And the mechanisms involved in MCR of colon cancer have not yet been studied.Objectives: 1. To construct the MCR model with colon carcinoma cells. 2. To explore the effect of NF-κB signaling pathway on MCR of colon carcinoma cells and its...