[Effect and mechanism of Yueju Pills on breast cancer induced by DMBA in rats].

This paper aims to explore the inhibitory effect of Yueju Pills on breast cancer and decipher the underlying mechanism. A total of 92 SPF-grade SD female rats were involved in this study, and 14 of them were randomly selected into control group. The remaining 78 rats were administrated with 7,12-dimethylbenzanthracene(DMBA) by gavage to establish the breast cancer model. The modeled rats were randomized into model, tamoxifen(1.9 mg·kg~(-1)·d~(-1)), and low-and high-dose(17, 34 g·kg~(-1)·d~(-1)) Yueju Pills groups. The mental state, food intake, and activities of the rats were observed daily, and the body weight was measured on alternate days. After 12 weeks of administration, the rats were sacrificed and the tumor weight was measured. The serum estrogen and progeste-rone levels were determined by enzyme-linked immunosorbent assay. The histopathological changes of the breast and tumor were observed by hematoxylin-eosin staining. Western blot was employed to measure the protein levels of glucose transporter 1(GLUT1), lactate dehydrogenase A(LDHA), phosphofructokinase muscle(PFKM), pyruvate kinase isozyme type M2(PKM2), hexokinase 2(HK2), nuclear factor-kappaB(NF-κB), and phosphorylated NF-κB. The intestinal microbiome was examined by 16S rRNA high-throughput sequencing. The results showed that compared with the model group, high and low-dose Yueju Pills showed the tumor inhibition rate of 15.8% and 64.5%, respectively, and the low dose group had stronger inhibitory effect. Compared with the control group, the model group presented elevated the levels of estrogen and progesterone in serum. The administration of Yueju Pills lowered such ele-vation, and the low-dose group showed stronger lowering effect(P<0.05). Compared with the model group, Yueju Pills reduced the glands with increased breast tissue, the degree of breast duct expansion, the number and area of acinar cavity, the secretions, and the layers of mammary epithelial cells. Furthermore, Yueju Pills down-regulated the expression of GLUT1, LDHA, PFKM, PKM2, HK2, and NF-κB(P<0.05) and altered the diversity, composition, structure, and abundance of intestinal flora. The results showed that Yueju Pills could inhibit breast cancer by regulating the secretion of estrogen and progesterone, glycolysis, inflammatory cytokines, and intestinal flora.

RNA-Seq Analysis Reveals Dendrobium officinale Polysaccharides Inhibit Precancerous Lesions of Gastric Cancer through PER3 and AQP4.

PURPOSE: There has been mounting evidence that Dendrobium officinale polysaccharides (DOP), a traditional Chinese medicine, are a potential candidate treatment for N-methyl-N'-nitro-N-nitrosoguanidine- (MNNG-) induced precancerous lesions of gastric cancer (PLGC). However, the underlying mechanisms have not been adequately addressed. METHOD: We utilized RNA-Seq analysis to investigate possible molecular targets and then used Venn software to identify the differentially expressed genes (DEGs). Further, we analyzed these DEGs with core analysis, upstream analysis, and interaction network analysis by IPA software and validated the DEGs by real-time PCR and Western blot. RESULT: 78 DEGs were identified from the normal control group (CON), the PLGC model group (MOD), and the DOP-treated group (DOP) by the Venn software. Further analysis of these DEGs, including core analysis, upstream analysis, and interaction network analysis, was performed by Ingenuity Pathway Analysis (IPA). The main canonical pathways involved were SPINK1 Pancreatic Cancer Pathway (-log (P value) = 4.45, ratio = 0.0667) and Circadian Rhythm Signaling (-log (P value) = 2.33, ratio = 0.0606). Circadian Rhythm Signaling was strongly upregulated in the model group versus the DOP group. CLOCK was predicted to be strongly activated (z-score = 2.236) in upstream analysis and induced the downstream PER3. In addition, the relative mRNA expression levels of seven DEGs (CD2AP, ECM1, AQP4, PER3, CMTM4, ESRRG, and KCNJ15) from RT-PCR agreed with RNA-Seq data from MOD versus CON and MOD versus DOP groups. The gene and protein expression levels of PER3 and AQP4 were significantly downregulated in the PLGC model and significantly increased by DOP treatment (9.6 g/kg). CONCLUSIONS: These findings not only showed DOP inhibits PLGC development by upregulating the PER3 and AQP4 gene and protein expression but also suggested that its mechanism of action involved modulating the Circadian Rhythm Signaling pathway.

The effect and mechanism of YH0618 granule on chemotherapy- induced hair loss in patients with breast cancer: study protocol for a randomized, double-blind, multi-center clinical trial.

BACKGROUND: Hair loss is one of the most common side effects of chemotherapy, and can cause persistent negative emotions, further affecting therapeutic effects and reducing the quality of life. However, there are no clinically safe and effective methods to solve the problem at present. Our previous clinical and animal studies showed that a medicinal and edible decoction, YH0618, could significantly promote hair growth in cancer patients after chemotherapy, without interfering with the anti-tumor effects of chemotherapy. Besides, the theory of Chinese Medicine believes that the "Essence of the kidney is reflected on the hair". Therefore, this study will further explore the efficacy of YH0618 granule on chemotherapy-induced hair loss in patients with breast cancer by a randomized, double-blind, multi-center clinical trial and elucidate the potential mechanism from the aspect of kidney deficiency or renal dysfunction. METHODS/DESIGN: Eligible breast cancer patients who will start chemotherapy will be randomly divided into group A (YH0618 granule) and group B (placebo). The chemotherapeutic agents contain taxanes or/and anthracyclines, and the chemotherapy regimen will be for at least six cycles with a cycle every 3 weeks. Subjects assigned to group A will receive YH0618 granules twice a day (6 g each time), 6 days a week, mixed with 300 ml warm water from the first to the fourth chemotherapy cycle. Subjects in group B will receive the placebo granule in the same manner. The primary outcome is the time point of occurrence of hair loss reaching grade II as assessed by the WHO Toxicity Grading Scale, and objective indices of hair quality and hair-follicle growth recorded by a hair and scalp detector before the fifth chemotherapy cycle. Secondary outcomes include changes of facial color and thumbnail color, grading of thumbnails ridging, assessment of quality life, level of fatigue, routine blood test results, hepatic and renal function, and certain medical indicators which can reflect kidney deficiency in Chinese Medicine. DISCUSSION: This research is of great significance for the treatment of cancer and improving the quality of life of cancer patients. The study may provide the most direct evidence for meeting clinical needs and lay a solid scientific foundation for later product development. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ID: ChiCTR1800020107. Registered on 14 December 2018.

Effect of Dendrobium officinale Extraction on Gastric Carcinogenesis in Rats.

Dendrobium officinale (Tie Pi Shi Hu in Chinese) has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg) were orally administered to the rats of the gastric carcinogenesis model. Compared with the cancer model group, the high dose of Dendrobium officinale extracts significantly inhibited the rate of carcinogenesis. Further analysis revealed that Dendrobium officinale extracts could regulate the DNA damage, oxidative stress, and cytokines related with carcinogenesis and induce cell apoptosis in order to prevent gastric cancer.