Figure 5.

Propofol attenuated chemotherapy-resistance development induced by isoflurane exposure via inhibition of HIF-1α in human prostate cancer cells. (A) Exposure to 2% isoflurane induced resistance against docetaxel (an anti-mitotic chemotherapy medication), shown as positive staining for Ki67, a marker for active mitosis (mean±s.d., n=8; **P<0.001 vs docetaxel; ^##P<0.001 vs isoflurane+docetaxel); (B) MTT assay also demonstrated that with isoflurane pre-treatment, cells had a higher proliferation rate, which was prevented with propofol (mean±s.d., n=6; **P<0.01 vs docetaxel; ^#P<0.05 vs isoflurane+docetaxel); (C) cytochrome-c release, as a marker of cellular injury caused by decetaxel treatment, was reduced in isoflurane-exposed cells, while treatment with propofol at 4 μg ml⁻¹ or HIF-1α-specific siRNA (20 nM) restored the sensitivity to Dectaxel treatment; (D) anti-apopotic protein, Bcl-2 was also overexpressed following isoflurane exposure before chemotherapy challenge. All these changes in favour of cell survival were blocked by co-administration of propofol at 4 μg ml⁻¹ or HIF-1α-specific siRNA (20 nM) with isoflurane (n=4; **P<0.001 vs naïve control; ^##P<0.001 vs isoflurane alone). Abbreviations: Doc=docetaxel; Iso=isoflurane; Pro=propofol. Bar=50 μm.