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Tumor Discovery HHT inhibits pancreatic cancer progress

A C

B D

E F

Figure 6. Toxicity evaluation and therapeutic effects of HHT on pancreatic cancer in vivo. (A) Body weight of healthy mice received intravenous
administration of HHT at four dosages including 0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg, and 4.0 mg/kg (once per day for 4 days) (n = 3). (B) Numbers of
surviving mice after receiving the treatment described in panel A. (C) Tumor volume growth curve for each group. The tumor-loading mice were given
a 2-week treatment. Each week, HHT at 0.5 mg/kg and 1.0 mg/kg were administered once per day for five consecutive days, followed by a 2-day break.
(D) Body weight change curve for the three groups. (E) Representative tumor images from each group after 2 weeks of HHT treatment. On the day 16, all
tumors were collected and analyzed. (F) Tumor weights of mice in each group (n = 7). Note: *P < 0.05, ***P < 0.001.
Abbreviations: HHT: Homoharringtonine; g: Gram.

3.5. HHT alleviated immunosuppressive status 4. Discussion
within the TME
PDAC is a highly invasive and deadly malignant tumor.
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To further assess whether HHT affected the TME, the Although current standard-of-care treatments such as
viability of RAW264.7 macrophages was examined using FOLFIRINOX (a combination of 5-fluorouracil, leucovorin,
the CCK-8 assay. It was shown that HHT treatment led irinotecan, and oxaliplatin) and gemcitabine with
to a dose-dependent reduction in macrophage viability nanoparticle albumin-bound paclitaxel (nab-paclitaxel)
(Figure 8A), with an IC50 of 52.33 nM. Immunofluorescence have achieved great progress in PDAC therapy, clinical
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staining indicated that the number of macrophages was outcomes remain unsatisfactory. Therefore, it is of great
reduced by the HHT treatment. In the control group, significance to develop more effective chemotherapeutic
a large amount of F4/80-positive macrophages (green drugs and understand their underlying mechanisms.
fluorescence) were distributed and surrounded the ductal
carcinoma structures. However, treatment with 1.0 mg/kg Previous studies have reported the inhibitory effects of
HHT significantly decreased the number of macrophages HHT on the proliferation of certain pancreatic cancer cell
in the tumor tissues (Figure 8B). lines, focusing primarily on signaling pathway activation

Volume 4 Issue 1 (2025) 107 doi: 10.36922/td.7825