The
relationship between human papillomavirus (HPV) and esophageal
cancer (EC) has been controversial, which may be caused by the difference
in geographic regions of sample origin. Thus, we conducted a case-control
study to find that HPV increased the risk of esophageal cancer, and
the HPV18 detection rate is the highest (24.2%) among patients with
EC, suggesting that HPV18 could be the most risk subtype of HPV infected.
We then identified high-risk HPV18 and N-methyl-N′-nitro-N-nitroso-guanidine (MNNG)
to establish a model on the viral etiology cooperating with environmental
carcinogens. Het-1A cells containing HPV18 were continuously exposed
to MNNG or not; then the morphological phenotype and function assays
were performed in 25th passage cells. MNNG promoted the proliferation
and invasion abilities and inhibited apoptosis both in Het-1A-HPV18
and control group. However, the Het-1A-HPV18 had a stronger change
in phenotypic features and formed more transformed foci in soft agar.
Further, Western blot found p53 and p21 were down-regulated, and expression
of c-Myc, MMP-2, and MMP-9 and Bcl-2/Bax ratio were up-regulated.
Our results revealed that MNNG was easier to induce malignant transformation
of Het-1A cells transfected with HPV18. It is good evidence for the
close relationship between HPV and the etiology of EC, providing foundation
for further study in molecular mechanism and specific intervention
targets.