Autophagy is one of the major pathways for degradation of
cellular components in animal cells that controls the turnover of
long-lived proteins and organelles. Although initially identified as
a process induced by cellular starvation, an autophagic pathway
is now recognized as the cellular response to a variety of stimuli
including starvation, hormone treatment, virus infection and
various stress conditions. It is unclear yet about the relationship between autophagy and malignancies, mostly it relies on the
type of malignancy. Autophagy acts in both cancer progression
and suppression. Recent studies show that the autophagy and
apoptosis pathways are regulated by common factors, share
common components and exert overlapping functions. For
example, the blockage of autophagic signals increases apoptosis,
whereas the inhibition of apoptosis may result in an autophagic
programmed cell death.
Prostate cancer is very common in Western populations
and is the second leading cause for male death from cancer
in North America. In recent years, the morbidity of prostate
cancer in China and other Asian countries has been also steadily
rising. Androgen plays a critical role in the development and
progression of prostate cancer. However, the regulatory role
of androgen in the autophagic process and the function of the
increased autophagosomes following androgen deprivation
remain poorly understood. We found that autophagosomes,
which were induced upon serum deprivation in LNCaP cells,
can be significantly suppressed by dihydrotestosterone.
(DHT). Pharmacological inhibition of autophagy by
3-methyladenine led to increased apoptosis of LNCaP cells in
serum-free medium compared to the medium with DHT or
serum. Additionally, depletion of Beclin 1 to inhibit autophagy
by small interfering RNA resulted in a slower proliferation
of LNCaP cells in the medium depleted of serum than in the
medium with DHT.
Altogether, these findings suggested that LNCaP cells can
resort to the autophagic pathway to survive under androgen
deprivation conditions, which can be a novel mechanism
involved in the transition of prostate cancer cells from an
androgen-dependent to an androgen-independent cell type.
Bladder cancer is the most common urinary cancer in China.
Cisplatin- based chemotherapy has shown the survival benefit
for the patients, but cisplatin-resistance renders the effect of
chemotherapy. The mechanism of chemo-resistance is still
unknown. We have found that cisplatin could cause autophagy
on bladder cancer cells (T24) while the apoptosis triggered.
The regulation autophagy process directly monitored the
apoptosis program and its signal pathway. The results implied the
connection between autophagy and apoptosis during bladder
cancer chemotherapy. These results prospected the manipulated
the autophagy to reduce the chemo-resistance on cisplatin.
It is well known that the VHL gene plays a definite role in
the tumor genesis of Renal Cell Carcinoma. The growth factor
receptors targeted therapy came to the clinical and showed
good efficacy in recent years. Our research group has found the
autophagy change between the tumor tissue and adjacent normal
tissue. The mTOR signal pathway may play a dominant function on autophagy process. Our oncoming research will focus on
EGF and VEGF signal pathway on autophagy and its internal
relationship with mTOR and autophagy.