Qingyihuaji formula reverses gemcitabine resistant human pancreatic cancer through regulate lncRNA AB209630/miR-373/EphB2-NANOG signals

Abstract

To investigate the possible mechanism of Qingyihuaji formula (QYHJ) for reversing gemcitabine (GEM) resistant human pancreatic cancer. Cell proliferation, apoptosis, migration and invasion were detected in CFPAC-1 cells. Xenograft mice established with CFPAC-1 through subcutaneous on 33 immunodeficient nude mice and randomly divided into four groups: vehicle, GEM (35 mg/kg), QYHJ (40 g/kg), and GEM + QYHJ (35 mg/kg + 40 g/kg) groups for 28-day treatment. Tumor growth and the mRNA expression of lncRNA AB209630, miR373, EphB2, and NANOG evaluated in dissected tumor tissue by real-time PCR, the CD133+ cancer stem cells were isolated by flow cytometer, and the changes of the tumor sphere forming were measured. QYHJ, especially the combination of GEM and QYHJ, was significantly inhibited the cell proliferation and migration of CFPAC-1 in vitro in the indicated times. The combination of GEM and QYHJ also remarkably promoted the cell apoptosis of CFPAC-1. QYHJ treatment effectively blocked the tumor growth in nude mice. QYHJ, especially GEM + QYHJ treatment, was significantly increased the mRNA expression of lncRNA AB209630, significantly decreased the mRNA levels of miR373, EphB2 and NANOG, and markedly reduced the tumor sphere formation and the numbers of CD133+ stem cells. In addition, GEM alone treatment had no significant effect in the above biomarker changes. QYHJ could effectivly enhance the antihuman pancreatic tumor activity of GEM, which may be through inhibiting pancreatic cancer stem cell differentiation by lncRNA AB209630/miR-373/EphB2-NANOG signaling pathway.

Integrated Analyses Identify Immune-Related Signature Associated with Qingyihuaji Formula for Treatment of Pancreatic Ductal Adenocarcinoma Using Network Pharmacology and Weighted Gene Co-Expression Network

“…Accumulating evidence suggested that TCM contributes to treating multifarious diseases, including malignancies [8,9]. The novel TCM formula Qingyihuaji (QYHJ) is produced by professor Luming Liu, which composed of Banzhilian (Herba Scutellariae Barbatae, HSB), Baihuasheshecao (HerbaHedyotdis, HBHY), Tiannanxing (Rhizoma Arisaematis erubescentis, RAE), Jiaogulan (Herba seu Radix Gynostemmatis pentaphylli, HSRGP), and Doukou (Fructus Amomi Rotundus, FAR), which was widely used for the treatment of PC during the past decades [10][11][12]. Besides, our previous clinical studies suggested that QYHJ treatment combined with first-line clinical western medicine improves the survival of PC patients with liver metastases [11,13].…”

Huaier increases the antitumor effect of gemcitabine on pancreatic cancer in vitro and in vivo

“…The combination of some TCM extracts and gemcitabine are also reported to have better antitumor effects in pancreatic cancer therapy than gemcitabine alone. Oridonin was shown to overcome gemcitabine resistance in PANC-1/Gem cells (24), and melittin, Qingyihuaji formula (QYHJ) and curcumin have been demonstrated to promote gemcitabine sensitivity in human pancreatic cancer treatment (25)(26)(27). However, to the best of our knowledge, the anticancer effect of the combination of Huaier and gemcitabine has not been reported.…”

MicroRNAs and Long Non-Coding RNAs as Regulators of NANOG Expression in the Development of Oral Squamous Cell Carcinoma

“…Similarly, studies on hepatocellular carcinoma and on pancreatic ductal adenocarcinoma showed AB209630 down-regulation in tumor samples compared to adjacent tissue ( 46 , 47 ). Published data indicate a possible correlation between the expression of NANOG and AB209630 in human pancreatic cancer cells ( 21 ). To the best of our knowledge, this is the first study on the expression of AB209630 in OSCC carcinogenesis.…”

“…Certain lncRNAs have already been shown that have potential to influence stemness-associated transcription factors, including NANOG ( 22 ). Based on the literature search, we selected RoR, SNHG1 and AB209630 , which were experimentally validated that either sponge miR-145 and miR-34a or directly or indirectly influence NANOG expression ( 19 – 21 ). Additionally, we analyzed the expression level of TP53 since it is a connection point in the regulation of selected ncRNAs ( 23 – 25 ).…”

“…First, we selected 13 miRNAs that could target NANOG in different cell lines using online databases TarBase v.8 ( 17 ) and miRTarBase ( 18 ), with inclusion criteria based on validation method. Next, we used literature search for selection of lncRNAs, which are experimentally validated that either sponge selected miRNAs or directly or indirectly influence NANOG expression ( 19 – 21 ). Based on the expression accuracy, we chose two miRNAs for further analysis, i.e.…”