Insulin-like growth factor (IGF) and its receptor (IGF-IR) play an important role in mitogenesis, apoptosis, growth, and proliferation of several types of cancers. Overexpression of IGF-IR in colorectal cancer is associated with increase of cancer cell proliferation and migration as well as inhibition of apoptosis. In our previous reports we demonstrated correlations between IGF-IR and apoptosis. Moreover, we observed relationships between connexin26 (Cx26) expression and apoptotic markers in human colorectal cancer. Recently, it has been shown that expression of connexins and gap junction (GJ) functions are also regulated by growth factors, including IGF-I. Therefore, in this study we have focused on the relationships between IGF-IR and Cx26 as well as Bcl-xL expression. A total number of 115 cases of colorectal cancer were examined by immunohistochemistry, using the avidin-biotin-peroxidase method. Associations among the above proteins were assessed in the entire group of colorectal cancer patients and its subgroups, depending on lymph node involvement (N0 and N1), histological grade (G2 and G3), extent of tumor growth (pT1+pT2 and pT3+pT4), histopathologic type (adenocarcinoma and mucinous carcinoma), sex, age (<or=60 and>60), and tumor site (colon and rectum). The expression of IGF-IR, Cx26, and Bcl-xL was noted in 47%, 56.5%, and 75.6% of the tumors, respectively. In the entire group of patients we found a positive correlation between IGF-IR and Cx26 (P<0.0001, r=0.374) as well as between IGF-IR and Bcl-xL (P<0.0001, r=0.344). Our results may suggest that the insulin-like growth system is involved in regulation of apoptosis and probably connexin expression in colorectal cancer cells.