BackgroundColorectal cancer (CRC) is a major burden of public health and healthcare worldwide. Microbiota has been suggested in promoting chronic inflammation in the intestine which, in turn, promotes tumor development. This study focuses on possible correlations of human papillomavirus (HPV) infection with proinflammatory Stat3 signaling activities and the resulting levels of its downstream proinflammatory cytokine IL-17 in CRC patients.MethodsHPV was examined using HPV Genotyping Chip technology and constitutively active Stat3 (p-Stat3) and IL-17 levels were tested using immunohistochemistry (IHC) in paraffin-embedded cancerous and adjacent normal tissues (ANT) from a cohort of 95 CRC patients. Correlation analyses were performed between HPV infection and clinicopathological characteristics, Stat3 activities and IL-17 levels among these CRC patients.ResultsThree major findings were observed: (1) HPV infection existed in a high rate of CRC cases (48.4%, 46/95), of which 45 cases (45/46, 97.8%) were high-risk HPV16-positive and only one case was HPV53-positive. (2) HPV infection correlated with poorer clinical stages (III+IV) of CRC. (3) HPV infection strongly correlated with both constitutively higher Stat3 activities (P<0.01) and higher IL-17 levels (P<0.01) only in CRC tissues but not in ANT tissues.ConclusionsHPV infection is common in CRC patients suggesting potentially preventive effectiveness of HPV vaccination among high-risk young individuals. We have for the first time revealed a tri-lateral relationship among HPV infection, constitutive Stat3 activity and IL-17 level, whose collaborative act may orchestrate a proinflammatory microenvironment in the colorectum that, in turn, may promote carcinogenesis and possibly facilitate progression of CRC.
Defects in apoptotic machinery vary among individual cancer cells, and the efficacy of chemotherapy in killing cancer cells depends on the successful induction of apoptosis. This study tested the hypothesis that the intrinsic ability of a cancer cell's natural resistance to apoptosis would indicate its ability in resistance to chemotherapy. Four widely studied human colorectal cancer cell lines, SW480, HT-29, LoVo and Caco-2, were examined for their apoptotic fates in spontaneous cultures for up to 6 days using flowcytometry. Chemoresponse of these cells was tested against anti-colorectal cancer drugs 5-fluorouracil (5-FU) and oxaliplatin (OXP) at different peak plasma concentrations (PPCs) using MTT assay. Apoptosis analyses demonstrated that, from Day 2 to Day 6 in spontaneous cultures, SW480 and HT-29 lines showed resistance to apoptosis by having much less average early and late apoptotic cells than LoVo and Caco-2 lines with differences of 3.2- to 5.2-fold. Interestingly, apoptosis-resistant SW480 and HT-29 exhibited higher chemoresistance to both 5-FU (P < 0.01 at 5×, 10×, and 50× PPC) and OXP (P < 0.01 at 5× and 10× PPC, and P < 0.05 at 50× PPC) than LoVo and Caco-2. Colorectal cancer cells' natural resistance to apoptosis is an intrinsic ability that correlates with resistance to chemotherapeutic drugs 5-FU and OXP. Cancer cells' natural apoptotic phenotypes may help predict the outcome of chemotherapy in colorectal cancers.
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