Small interfering RNA target for long noncoding RNA PCGEM1 increases the sensitivity of LNCaP cells to baicalein

Abstract

The objective of this study is to investigate the inhibitory effect and mechanism of long noncoding RNA PCGEM1 siRNA combined with baicalein on prostate cancer LNCaP cells. LNCaP cells transfected with small hairpin RNA lentiviral vector targeting PCGEM1 were constructed and their expression in LNCaP cells was absent. The stable cell line of LNCaP cells infected with LV3‐shRNA‐PCGEM1 was successfully constructed. In addition, LV3‐shRNA‐PCGEM1 was able to increase the baicalein‐induced inhibitory effects on LNCaP cells, and the susceptibility was 2.3 fold higher than that of baicalein alone. LV3‐shRNA‐PCGEM1 combined with baicalein also inhibited the colony formation, increased G2 and S phase cells, inhibited the expression of PCGEM1, and induced autophagy of LNCaP cells. In summary, LV3‐shRNA‐PCGEM1 may improve the sensitivity of LNCaP cells to baicalein, and the molecular mechanism may be associated with the decrease of PCGEM1 expression and the induction of autophagy. Our findings provided an experimental basis for the combined treatment of Chinese traditional and Western medicine on prostate cancer in a clinical setting.

Autophagy: Mechanisms and Therapeutic Potential of Flavonoids in Cancer

“…Baicalein inhibited the proliferation of MCF-7 and MDA-MB-231 breast cancer cells, Fro undifferentiated thyroid cancer cells, and MGC-803 gastric cancer cells, and induced apoptosis and autophagy. It downregulated the expression of downstream proteins phosphorylated Akt (p-AKT), phosphorylated mTOR (p-mTOR), NF-κB, and phosphorylation of inhibitor of kappa B (p-IκB), which play a regulatory role in autophagy, apoptosis, and tumor growth [ 50 , 51 , 146 ]. Drp1-dependent mitochondrial fission is an early and key event of apoptosis, while excessive division will lead to mitochondrial dysfunction, apoptosis, and autophagy.…”

H1Innovative approaches to combat anti‐cancer drug resistance: Targeting lncRNA and autophagy

“…silenced PCGEM1 in LNCaP prostate cells and treated them with baicalein. They found that reducing PCGEM1 expression enhanced the inhibitory effect of baicalein on tumor cell proliferation and colony formation, induced apoptosis and autophagy and increased the sensitivity of LNCaP cells to baicalein 58 . However, more research is needed to understand the relationship between PCGEM1, baicalein sensitivity or drug resistance and tumor cell autophagy, as well as the specific regulatory mechanism (Figure 5).…”

“…However, some researchers have also observed that autophagy was inhibited in DOX-resistant neuroblastoma, 56 paclitaxel (PTX)-resistant breast cancer 57 and baicalein-resistant prostate cancer. 58 There are many different types of anti-tumour drugs, including cytotoxic drugs that can affect DNA structure and function, interfere with nucleic acid biosynthesis, transcriptional processes, RNA synthesis and protein synthesis and function. There are also non-cytotoxic anti-tumour drugs, such as Tamoxifen (TAM), for ERpositive breast cancer and certain molecularly targeted drugs.…”

“…In most cases, lncRNA and/or drug‐induced autophagy enhancement has been found to mediate drug resistance for 13 anti‐tumour drugs in at least 16 types of tumours. However, some researchers have also observed that autophagy was inhibited in DOX‐resistant neuroblastoma, 56 paclitaxel (PTX)‐resistant breast cancer 57 and baicalein‐resistant prostate cancer 58 …”

LncRNA PCGEM1 in Human Cancers: Functions, Mechanisms and Promising Clinical Utility

“…Because of the important roles by which PCGEM1 facilitates PC progression in an AR-dependent or AR-independent manner, PCGEM1-targeted treatment is also an attractive area of study. For example, PCGEM1 silencing could increase the sensitivity of PC cells to baicalein and enzalutamide ( 51 , 55 ), laying the groundwork for PC combination therapy. Further clinical trials are needed to design and assess the therapeutic effects of targeting PCGEM1.…”