Background:
Cancer stem cells (CSC) can be enriched by 3- dimensional culture techniques (Spheroids).
ALDH is regarded a ubiquitous CSC marker. It contributes to cancer drug resistance
due to its detoxificating property. ATRA is a downstream product of ALDH and is capable
to induce CSC differentiation. We observed the impact of ATRA or/and cisplatin on
ALDH expression in cervical cancer cell line-derived SDCs.
Materials and methods:
Cell lines, Hela, MRIH186, and SiHa were used to generate spheroids and subsequently
treated with different concentrations of ATRA or/and cisplatin. ALDH expression was
evaluated after 72h drug administration using ALDEFLUOR kit by flow cytometry. The
mRNA expression of ALDH isotypes was detected by real time PCR.
Results:
Compared to the corresponding monolayer cells, the spheroid-derived cells showed higher
ALDH+ cell frequency (5.12-, 1.89-, 1.85-fold up-regulated Hela, MRIH186, and SiHa,
respectively; p < 0.05). Upon treatment with different concentrations of ATRA, the
ALDH+ cell proportion showed a dose-dependent reduction in all cell lines. A bi-phasic
response was found after cisplatin treatment. At concentrations below its IC50, cisplatin increased ALDH+ frequency (1.83-, 1.67-, 2.04-fold in Hela, MRIH186, and
SiHa, respectively; p < 0.05). At higher cisplatin concentration ALDH+ cell frequency
was sharply reduced. Combined treatment with ATRA and cisplatin resulted in an enhanced
decline of ALDH expression. mRNA expression of ALDH1A1 and ALDH1A3 was reduced by
ATRA.
Conclusions:
ATRA can reduce ALDH+ cell frequency in cervical SDCs. The combination of ATRA with
cytotoxic drugs might be a promising strategy to overcome the chemo-resistance caused
by CSC.
