Targeting Cancer-Related Inflammation: Chinese Herbal Medicine Inhibits Epithelial-to-Mesenchymal Transition in Pancreatic Cancer

Abstract

Pancreatic cancer is an almost universally fatal disease resulting from early invasion of adjacent structures and metastasis and the lack of an effective treatment modality. Our previous studies have shown that Qingyihuaji Formula (QYHJ), a seven-herb Chinese medicine formula, had significant anti-cancer effects in pancreatic cancer. Here, we examined the effects of QYHJ on pancreatic cancer cell invasion and metastasis and the potential associated mechanism(s). We found that QYHJ inhibited both tumor growth and metastasis in nude mice with human pancreatic cancer cell xenografts. Further study indicated that QYHJ inhibited epithelial-to-mesenchymal transition (EMT), which is characterized by increased E-cadherin expression and decreased vimentin, N-cadherin and Slug expression. Interleukin 6 (IL-6), a pro-inflammatory cytokine produced mainly by macrophages, could promote cancer cell EMT and invasion. In contrast, treatment with QYHJ inhibited cancer-related inflammation in tumors by decreasing infiltration of tumor-associated macrophages and IL-6 production, thus preventing cell invasion and metastasis. These results suggested that the Chinese herbal medicine QYHJ could inhibit pancreatic cancer cell invasion and metastasis in part by reversing tumor-supporting inflammation.

Cryptotanshinone suppresses the proliferation and induces the apoptosis of pancreatic cancer cells via the STAT3 signaling pathway

“…The use of traditional Chinese herbs has exhibit beneficial effects in overcoming apoptosis resistance in pancreatic cancer (24). CPT, a biologically active compound from the root of Salvia miltiorrhiza, has exhibited significant anticancer effects in several tumor cells.…”

Nanog Predicts Poor Prognosis in Human Pancreatic Cancer and Is Downregulated by QingyihuaJi Formula in Pancreatic Cancer Stem Cells

“…QYHJ formula, comprised of seven Chinese herb medicines (Hedyotidis herba, Amorphophallus konjac , herba scutellariae barbatae, Coix seed, akebia stem, fiveleaf gynostemma herb, and java amomum fruit), was prepared as previously described [13–15]. In short, QYHJ powder was obtained from Jiangyin Tianjiang Pharmaceutical Co., Ltd. To ensure standardization and maintain the interbatch reliability of QYHJ, a high performance liquid chromatography (HPLC) chromatographic fingerprint was developed for quality control.…”

“…In short, QYHJ powder was obtained from Jiangyin Tianjiang Pharmaceutical Co., Ltd. To ensure standardization and maintain the interbatch reliability of QYHJ, a high performance liquid chromatography (HPLC) chromatographic fingerprint was developed for quality control. The fingerprint chromatograms of QYHJ formula are shown in our previous report [13–15]. The final decoction of QYHJ was prepared after dissolving the herbal powder in distilled water to the required concentration.…”

“…The daily dosage for nude mice was 36 g/kg, once per day p.o., respectively, calculated according to the following human-mouse transfer formula: D b = D a × ( R b / R a )×( W b / W a )2/3, where D , R , and W represent dosage, shape coefficient, and body weight, respectively, and a and b represent human and mouse, respectively. Gemcitabine (Eli Lilly) was dissolved in sterile PBS, 25 mg/kg [14, 15], twice per week by intraperitoneal injection. Antibodies of rabbit anti-human Nanog were purchased from Abcam.…”

Tipping Tumor Microenvironment against Drug Resistance

“…Meanwhile in this case, VEGF blockade may be concerned to complicate the vascular lesion triggered by ipilimumab [53,54]. Interestingly in parallel, certain traditional Chinese herb medicines, such as Qingyihuaji and Yanzheng Xiaoji, are recently emerging to show promising anti-tumor activities through inhibiting multitherapeutic targets and harmonizing disease-associated biological networks [55,56]. Moreover, Chinese herb medicines have been utilized in the clinic as an adjuvant treatment to alleviate the sideeffects resulted from anti-cancer chemo-and radio-therapies [57].…”