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. 2022 Jul 22:9:867575.
doi: 10.3389/fvets.2022.867575. eCollection 2022.

Antitumor Effects of Cannabinoids in Human Pancreatic Ductal Adenocarcinoma Cell Line (Capan-2)-Derived Xenograft Mouse Model

Siriwan Sakarin  1 , Nuntana Meesiripan  1 , Suleeporn Sangrajrang  1 , Nuntakan Suwanpidokkul  2 , Piyaporn Prayakprom  2 , Chatchada Bodhibukkana  2 , Vipada Khaowroongrueng  2 , Kankanit Suriyachan  3 , Somchai Thanasittichai  3 , Attasit Srisubat  4 , Pattamaporn Surawongsin  5 , Kasem Rattanapinyopituk  6
Affiliations

Antitumor Effects of Cannabinoids in Human Pancreatic Ductal Adenocarcinoma Cell Line (Capan-2)-Derived Xenograft Mouse Model

Siriwan Sakarin et al. Front Vet Sci. .

Abstract

Background: Pancreatic cancer is considered a rare type of cancer, but the mortality rate is high. Cannabinoids extracted from the cannabis plant have been interested as an alternative treatment in cancer patients. Only a few studies are available on the antitumor effects of cannabinoids in pancreatic cancer. Therefore, this study aims to evaluate the antitumor effects of cannabinoids in pancreatic cancer xenografted mouse model.

Materials and methods: Twenty-five nude mice were subcutaneously transplanted with a human pancreatic ductal adenocarcinoma cell line (Capan-2). All mice were randomly assigned into 5 groups including negative control (gavage with sesame oil), positive control (5 mg/kg 5-fluorouracil intraperitoneal administration), and cannabinoids groups that daily received THC:CBD, 1:6 at 1, 5, or 10 mg/kg body weight for 30 days, respectively. Xenograft tumors and internal organs were collected for histopathological examination and immunohistochemistry.

Results: The average tumor volume was increased in all groups with no significant difference. The average apoptotic cells and caspase-3 positive cells were significantly increased in cannabinoid groups compared with the negative control group. The expression score of proliferating cell nuclear antigen in positive control and cannabinoids groups was decreased compared with the negative control group.

Conclusions: Cannabinoids have an antitumor effect on the Capan-2-derived xenograft mouse model though induce apoptosis and inhibit proliferation of tumor cells in a dose-dependent manner.

Keywords: Capan-2; cannabinoids; mouse; pancreatic cancer; xenograft tumor model.

PubMed Disclaimer

Conflict of interest statement

NS, PP, CB, and VK were employed by The Government Pharmaceutical Organization. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The percentage of tumor volume changes of mice in the negative control group, the positive control group (5-FU), and THC:CBD at dose of 1, 5, and 10 mg/kg BW.
Figure 2
Figure 2
Gross morphology of mice in the negative control group (A), the positive control group (5-FU) (B), and THC:CBD at the dose of 1 mg/kg BW (C), 5 mg/kg BW (D), and 10 mg/kg BW (E), (scale bar = 1 cm). Tumor mass was presented subcutaneously with ulcerated and necrosis in several mice (arrow).
Figure 3
Figure 3
Histopathological morphology of mice in the negative control group (A), the positive control group (5-FU) (B), and THC:CBD at dose of 1 mg/kg BW (C), 5 mg/kg BW (D), and 10 mg/kg BW (E), (HE, 2×). Tumor masses were presented with necrotic tissue (N). Necrotic tissues were presented in the center and at the edge of the tumor especially in treatment and positive control groups compared with the negative control group.
Figure 4
Figure 4
Histopathological morphology of mice in the negative control group (A), the positive control group (5-FU) (B), and THC:CBD at dose of 1 mg/kg BW (C), 5 mg/kg (D), and 10 mg/kg (E), (HE, 40×).
Figure 5
Figure 5
Histopathological morphology of pancreatic adenocarcinoma of mice gavaged with THC:CBD. The tumor demonstrated scattered apoptotic cells (arrow) with necrotic tissue (N) (A) (HE, 20×). The graph demonstrated the average apoptotic cells per high-power field in the negative control group, the positive control group (5-FU), and THC:CBD at the dose of 1, 5, and 10 mg/kg BW. Data were expressed as mean ± SD. a indicates a significant difference at P < 0.05 compared to the negative control group. b indicates a significant difference at P < 0.05 compared to the positive control group (5-FU) (B).
Figure 6
Figure 6
The expression score of PCNA in tumor (A) score = 1, (B) score = 2, (C) score = 3, and (D) score = 4 (counterstained with Mayer's hematoxylin, 40×). The graph demonstrates the expression score of PCNA in the negative control group, the positive control group (5-FU), and THC:CBD at the dose of 1, 5, and 10 mg/kg BW. Data were expressed as mean ± SD. a indicates a significant difference at P < 0.05 compared to the negative control group (E).
Figure 7
Figure 7
Caspase-3 expression in the negative control group (A), the positive control group (5-FU) (B), and THC:CBD at the dose of 1, 5, and 10 mg/kg BW (C–E), respectively. Caspase-3 positivity is presented by brown color (arrows) (counterstained with Mayer's hematoxylin, 40×). The graph demonstrates the average number of caspase-3 positive cells per high-power field in the negative control group, the positive control group (5-FU), and THC:CBD doses of 1, 5, and 10 mg/kg BW. Data were expressed as mean ± SD. a indicates a significant difference at P < 0.05 compared to the negative control group. b indicates a significant difference at P < 0.05 compared to the positive control group (5-FU) (F).
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