Affiliations: [a] Department of Emergency, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu, China | [b] Department of Oncology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu, China
Correspondence:
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Corresponding author: Dong Shen, Department of Oncology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin 214400, Jiangsu, China. E-mail:[email protected]
Abstract: Breast cancer is currently the most common malignancy
affecting women worldwide. It had been shown that the allopregnanolone
biosynthesis was associated with tumorigenesis and PK11195, the Translocator
Protein 18 KDa (TSPO) antagonist, had the effects of the allopregnanolone
biosynthesis. However, little is known about the association between the
effects of PK11195 on the breast cancer and the allopregnanolone
biosynthesis. To evaluate this, the breast cancer cell lines MCF-7 and T47D
were cultured. Cell viability and proliferation were determined by CCK-8
assay. The IC50 of PK11195 on the MCF-7 and T47D were 5.4 nM and 6 nM. The
cell viability and proliferation of AC-5216 (TSPO selective ligand, 3 and 6 nM)
was blocked by PK11195 (5.4 nM and 6 nM). Moreover, we evaluated the role
of allopregnanolone biosynthesis in the effects of TSPO on breast cancer.
Enzyme-Linked ImmunoSorbent Assay (ELISA) was used in the measurement of the
allopregnanolone level. We found that the allopregnanolone level was
increased by AC-5216 (3 and 6 nM) and the increase was reversed by PK11195
(5.4 nM and 6 nM, resepectively) in MCF-7 and T47D. The TSPO mRNA level was
determined by real time polymerase chain reaction (PCR). The TSPO mRNA level
were increased by AC-5216 (6 nM), which the increases were reversed by
PK11195 (5.4 nM and 6 nM, resepectively) in MCF-7 and T47D. Collectedly, it
firstly indicated that the effects of PK11195 on MCF-7 and T47D were
associated with the decrease of allopregnanolone biosynthesis, which was
mediated by TSPO.
