Abstract:

Objective To investigate the effects of ganoderma lucidum ethanol extract （GLEE） on the biological behavior and Janus kinase 1（JAK1）/signal transduction and transcription activator 3 （STAT3） signaling pathway of the cervical cancer cells， and to clarify its possible mechanisms. Methods The human cervical cancer HeLa cells were randomly divided into control group （given complete culture medium） and low， medium and high doses of GLEE groups（given 25， 50， and 100 mg·L^－1 GLEE）. The inhibitory rates of proliferation of the human cervical cancer HeLa cells in various groups were detected by MTT assay； the clone formation rates of the human cervical cancer HeLa cells in various groups were detected by plate cloning experiment； Transwell chamber assay was used to detect the numbers of migration cells and invasion cells in various groups； the expression levels of JAK1 and STAT3 mRNA in the human cervical cancer HeLa cells in various groups were detected by real-time fluorescence quantitative PCR （RT-qPCR） method； the expression levels of JAK1， phophorylated JAK1（p-JAK1），STAT3， phophorylated STAT3（p-STAT3）， suppressor of cytokine signaling 3（SOCS3）， and protein inhibitor of activated STAT1 （PIAS1） proteins in the human cervical cancer HeLa cells in various groups were detected by Western blotting method. Results Compared with control group， the inhibitory rates of proliferation of the cervical cancer HeLa cells in low， medium and high doses of GLEE groups were increased （P<0.05），the clone formation rates the cervical cancer HeLa cells were decreased （P<0.05），the numbers of migration cells were decreased （P<0.05）， the numbers of invasion cells were decreased （P<0.05），the expression levels of JAK1 and STAT3 mRNA in the cervical cancer HeLa cells were decreased （P<0.05）， and the expression levels of SOCS3 and PIAS1 proteins in the cervical cancer HeLa cells were increased（P<0.05）. Compared with low dose of GLEE group， the inhibitory rates of proliferation of the cervical cancer HeLa cells in medium and high doses of GLEE groups were increased （P<0.05）， the clone formation rates of the cervical cancer HeLa cells were decreased （P<0.05）， the numbers of migration cells were decreased （P<0.05），the numbers of invasion cells were decreased （P<0.05）， the expression levels of JAK1 and STAT3 mRNA in the cervical cancer HeLa cells were decreased （P<0.05），and the expression levels of SOCS3 and PIAS1 proteins in the cervical cancer HeLa cells were increased （P<0.05）. Compared with midium dose of GLEE group， the inhibitory rate of proliferation of the cervical cancer HeLa cells in high dose of GLEE group was increased （P<0.05），the clone formation rate of the cervical cancer HeLa cells was decreased （P<0.05），the number of migration cells was decreased （P<0.05），the number of invasive cells was decreased （P<0.05）， the expression levels of JAK1 and STAT3 mRNA in the cervical cancer HeLa cells were decreased （P<0.05），and the expression levels of SOCS3 and PIAS1 proteins in the cervical cancer HeLa cells were increased （P<0.05）. Conclusion GLEE can inhibit the proliferation， cloning， migration and invasion of the cervical cancer HeLa cells to some extent， which may play a role by up-regulating the expression levels of SOCS3 and PIAS1 in the cells， thereby affecting the JAK1/STAT3 signaling pathway.

Key words: Ganoderma lucidum ethanol extract, Cervical neoplasms, Janus kinase 1, Signal transduction and transcription activator 3, Cytokine signaling inhibitor protein 3